DUBAI (Reuters) – Iranian and U.S. negotiators resumed talks on Friday in Rome to resolve a decades-long dispute over Iran‘s nuclear ambitions, Iranian media reported, despite Tehran warning that a new deal might not be possible amid mutually exclusive demands.

The stakes are high for both sides. President Donald Trump wants to curtail Tehran’s potential to produce a nuclear weapon that could trigger a regional nuclear arms race and perhaps threaten Israel. The Islamic Republic, for its part, wants to be rid of devastating sanctions on its oil-based economy.

Iranian Foreign Minister Abbas Araqchi and Trump’s Middle East envoy Steve Witkoff were expected to lead a fifth round of talks, through Omani mediators.

“This round of talks is especially sensitive … we need to see what issues will be raised by the other party … and based on that, we will proceed with our positions,” Iranian Foreign Ministry spokesman Esmaeil Baghaei told state TV in Rome.

Both Washington and Tehran have taken a tough stance in public over Iran‘s intensifying uranium enrichment program, which could potentially give it scope to build a nuclear warhead, even though Tehran says it has no such ambitions and the purposes are purely civilian.

Iran insists the talks are indirect, but U.S. officials have said the discussions – including the latest round on May 11 in Oman – have been both “direct and indirect”.

Ahead of the talks, Araqchi wrote on X: “…Zero nuclear weapons = we Do have a deal. Zero enrichment = we do NOT have a deal. Time to decide.”

White House press secretary Karoline Leavitt told reporters on Thursday that Trump believes negotiations with Iran are “moving in the right direction”.

U.S. Secretary of State Marco Rubio said on Tuesday that Washington was working to reach an accord that would allow Iran to have a civil nuclear energy program but not enrich uranium, while admitting that this “will not be easy”.

Iranian Supreme Leader Ayatollah Ali Khamenei, who has the last say on matters of state, rejected demands to stop refining uranium as “excessive and outrageous”, warning that such talks were unlikely to yield results.

Among remaining stumbling blocks is Tehran’s refusal to ship abroad its entire stockpile of highly enriched uranium – possible raw material for nuclear bombs – or engage in discussions over its ballistic missile program, which could carry warheads over long distances.

Iran says it is ready to accept some limits on enrichment, but needs watertight guarantees that Washington would not renege on a future nuclear accord.

Mounting Tensions

Trump in his first term in 2018 ditched a 2015 nuclear pact between major powers and Iran. Since returning to office this year, he has restored a “maximum pressure” campaign on Tehran and reimposed sweeping U.S. sanctions that continue to hobble the Iranian economy.

Iran responded by escalating enrichment far beyond the 2015 pact’s limits.

Wendy Sherman, a former U.S. undersecretary who led the U.S. negotiating team that reached the 2015 agreement, noted that Tehran presents enrichment as a matter of sovereignty.

“I don’t think it is possible to get a deal with Iran where they literally dismantle their program, give up their enrichment, even though that would be ideal,” she told Reuters.

The cost of failure of the talks could be high. Iran‘s arch-foe Israel sees Iran‘s nuclear program as an existential threat and says it would never allow the clerical establishment to obtain nuclear weapons.

Israel’s strategic affairs minister and the head of its foreign intelligence service, Mossad, will also be in Rome for talks with the U.S. negotiators, a source aware of the matter told Reuters.

Araqchi said on Thursday that Washington would bear legal responsibility if Israel attacked Iranian nuclear installations, following a CNN report that Israel might be preparing strikes.

Three Iranian sources said on Tuesday that the clerical leadership lacks a clear fallback plan if efforts to overcome the standoff collapse.

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(Reporting by Parisa Hafezi in Dubai and John Irish in Paris; writing by Parisa Hafezi; editing by Alexandra Hudson, Mark Heinrich and Kevin Liffey)