While in exile Leon Trotsky lived in the Coyoacán area of Mexico City at the home of the painter Diego Rivera and Rivera's wife and fellow painter, Frida Kahlo, with whom Trotsky had an affair.

After an ineffectual first attempt to have Trotsky murdered Stalin assigned the overall organisation of implementing the task to the NKVD officer Pavel Sudoplatov. According to Sudoplatov's Special Tasks, the NKVD proceeded to set up three NKVD agent networks to carry out the murder, one of which relied on Ramón Mercader.

On 24 May 1940, Trotsky survived a raid on his villa by armed assassins led by the NKVD agent Iosif Grigulevich and Mexican painter David Alfaro Siqueiros. Trotsky's young grandson was shot in the foot and a young assistant and bodyguard of Trotsky was abducted and later murdered, but other guards defeated the attack.

On 20 August Trotsky was attacked by Ramón Mercader who used a mountaineer's ice-axe as a weapon. The blow to his head was bungled and failed to kill Trotsky instantly. Witnesses stated that Trotsky spat on Mercader and began struggling fiercely with him. Hearing the commotion, Trotsky's bodyguards burst into the room and nearly killed Mercader, but Trotsky stopped them, laboriously stating that the assassin should be made to answer questions.Trotsky was taken to a hospital, operated on, and died as a result of loss of blood and shock.

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