The recent discovery that HTLV-I infected T-cells have an enhanced susceptibility to HTLV-III/LAV infection with concurrent cell lysis (S. Harada, Y. Koyanagi, and N. Yamamoto (1985) Science, 229, 563-566) led us to investigate a possible role for HTLV-II infected T cells in this respect. HTLV-II-bearing C3 cells were exposed to HTLV-III/LAV and the subsequent infection monitored by indirect immunofluorescence (IIF) of cells, reverse transcriptase (RT) activity in culture fluids, and hemacytometer cell counts. HTLV-III/LAV antigen expression was detected within 2 days whereas RT activity was detected within 3 days postinfection. The presence of immunofluorescent positive cells and RT activity was accompanied by cell lysis. Double infection of C3 cells was confirmed by IIF using a goat polyclonal antibody directed against the core p24 protein for detecting HTLV-II, and high titer serum from a pre-AIDS patient for detecting HTLV-III/LAV. We conclude that HTLV-I and HTLV-II infected T-cells share an enhanced susceptibility to HTLV-III/LAV infection with the promotion of cell lysis.