A statement released by Interpol on Sunday said that Meng has resigned with immediate effect. It did not say why.
Meng's wife said he had traveled back to China for work, after a visit to the Nordics.
Adding to the mystery, the global police agency tweeted Sunday night that it received Meng's resignation and that Kim Jong Yang of South Korea, a vice president representing Asia on Interpol's executive committee, would serve as acting president until Interpol's general assembly picks a permanent president next month.
Meng is a senior security official in China as well as the head of Interpol.
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The worldwide police agency Interpol announced Sunday that its missing president had resigned "with immediate effect" after China said the man was under investigation over unspecified legal violations and his wife told reporters that he had texted her an image of a knife, leading her to believe he was in danger.
His family last heard from him on September 25 and his whereabouts have been a mystery ever since. On Saturday, Interpol had demanded that China provide information about Meng's whereabouts, but officials in the country, which is now celebrating a week-long holiday, did not reply.
At a press conference on Sunday, she said that the last text message she had received from him was the image of a knife, which she took as a sign that he was in danger.
Her appearance at a press conference in Lyon, France, where Interpol's headquarters are based, came minutes before Beijing confirmed they had detained him as part of a criminal investigation.
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Meng is the first person from China to serve as Interpol's president, a post that is largely symbolic but powerful in status.
Local French media broadcast a video which they said was from Mr Meng's wife Grace, in which she issued a brief statement from a hotel in Lyon to express her concerns.
"As long as I can't see my husband in front of me, speaking to me, I can't have any confidence", Grace Meng was quoted as saying by French TV stations and Sunday newspapers. He was the first Chinese national to hold the position, which he was appointed to in 2016.
She said they were in daily contact during his trip before he went missing in China. She said Zhou had sought to muscle her husband out of the public security ministry - the national police force - several times and disliked her husband "very much", She did not explain what, if any, relation that animosity may now have with her husband's case.
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