Mehsud is the head of Tehrik-e-Taliban Pakistan, an umbrella organisation for groups operating across Pakistan's northwest.
His stronghold is South Waziristan, the scene of intense fighting between pro-Taliban fighters and Pakistani soldiers in recent months.
A commander close to Mehsud acknowledged that his boss had kidney problems, but denied that he had passed away.
He said he was on his way to Mehsud's headquarters in the town of Makeen to meet him.
Separately, a doctor for the Taliban and a spokesman for the group denied reports that Mehsud had fallen ill and died.
"I spoke to him today at 9am on the telephone, and he told me that he is surprised over rumours about his death," Eisa Khan, the physician told, The Associated Press news agency.
Officials have accused Mehsud of being behind a wave of suicide attacks in Pakistan since the middle of last year.
Pakistani and US officials have accused him of involvement in killing of Benazir Bhutto, the former prime minister and leader of the now ruling Pakistan People's Party, in a gun-and-bomb attack in December.
US missile strike
American officials express frustration at Pakistan's failure to kill or capture pro-Taliban leaders whom they accuse of sending fighters and arms into Afghanistan, where foreign troop casualties are escalating.
In a move that could help answer those complaints, Pakistan's army chief on Monday appointed a new head of the country's principal intelligence agency.
US and Afghan officials have accused elements in the Inter-Services Intelligence agency of secretly colluding with some armed groups.
The rumours of Mehsud's death coincide with a reported missile strike by a suspected US drone, killing at least six people in the tribal region near the Afghan border.
Two Pakistani intelligence officials said on Wednesday that the missiles struck the home of a local Taliban commander before Tuesday midnight near Mir Ali, a town in the North Waziristan region.
The officials, citing reports from their field agents, said at least six people were also wounded in the attack.
Both officials asked for anonymity because they were not authorised to speak to media.
They said a US drone aircraft - not Pakistani forces - fired the missiles.