The International Atomic Energy Agency said on Thursday that its senior and key nuclear inspector, Olli Heinonen, will be leaving his post at the end of August.
Heinonen, a deputy director, has headed the UN nuclear watchdog's all-important safeguards department, which is responsible, among other things, for making sure that nuclear material is not used for weapons.
As a deputy director, he is perhaps the most high-profile official at the Vienna-based agency after Director General Yukiya Amano, and over the course of his tenure has led sensitive Iran and Syria investigations. Both countries are suspected of hiding weapons-related nuclear activities.
"We confirm that Mr Heinonen informed the director general of his resignation for personal reasons to take effect at the end of August," IAEA spokeswoman Gill Tudor said.
"The director general has decided to respect his intention, with high appreciation for this long contribution to the agency."
She said no decisions have been made on a successor, but that the post would be filled without delay.
Heinonen, a Finnish radiochemist, joined the IAEA in 1983 and was appointed head of safeguards in July 2005.