Abrin A chain, alpha-sarcin, mitogillin, restrictocin and Phytolacca americana protein (PAP) all effectively inhibited protein synthesis in picornavirus-infected cells, although with different activities. The most powerful inhibitor was alpha-sarcin; 0.1 μM caused over 90% inhibition in virus-infected cells, whereas no inhibition of translation was observed in uninfected cells even at concentrations of 40 μM alpha-sarcin. Inhibition depended on the multiplicity of infection and concentration of toxin. Although the blockade of protein synthesis by alpha-sarcin was maximal when the toxin was added simultaneously with the virus, a drastic inhibition was also observed if this addition was made after virus entry, suggesting that the toxin passes into the cell once membrane permeability has been modified by viral infection. Inhibitors of transcription and translation did not suppress the entry of alpha-sarcin into the cell. This could indicate that a virion component is involved in the permeabilization of the cell to the toxin. However, heat-inactivated virions did not promote the permeabilization of the cell to alpha-sarcin. Our efforts to detect a toxin-virus complex were unsuccessful. Similar results were obtained with HeLa cells infected by adenovirus type 5 and with BHK cells infected by Semliki Forest virus.