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In 1988, Ponomaryov helped create the human rights organization Memorial.
In 1989, Ponomaryov filled the place of academic Andrei Sakharov in the Congress of People's Deputies of the Soviet Union after he died suddenly from a heart attack.
In 1997, Ponomaryov founded the Russian human rights society "For Human Rights" (Za prava cheloveka), becoming its executive director and a member of the Council on Motion.
Also in 1997, Ponomaryov was one of the founders of the "Hotline" (Goriachaia liniia) and founded and is one of the most active members of the group Common Action (Obshchee deistvie).
Ponomaryov took part in the Coordination Council of Moscow Union of Electors and in the initiative group for the creation of the Civil Action Committee.
In the autumn of 1991, he presided over the parliamentary commission for investigation of GKCh P activities and the KGB’s role in the 1991 Soviet coup d'état attempt.
On October 22, 2011 Ponomaryov was filmed by the Russian Federal Security Service while having a meeting with the Japanese ambassador, he assured the Japanese ambassador that he would advocate the Japanese claims for the Kuril Islands for a payment, which are a part of the Soviet Union and therefore Russia since the defeat of Imperial Japan in the Second World War.
In this case Ponomaryov would have to identify himself as a "foreign agent" according to new laws issued by Putin, which are based on the US Foreign Agents Registration Act issued in 1938.
The court obliged Ponomaryov to refute the unreliable information about Kalinin that he had made public.
He actively defended the ex-owner of YUKOS Mikhail Khodorkovsky and the other persons sentenced for economical offences in the YUKOS case, some human rights activists consider that these persons are persecuted for political reasons (making them political prisoners) and that the charges against them are fabricated.