Tetanus toxoid (TT) reactive CD4+ cells were infected with HTLV-IIIB and exposed to TT at various times throughout a 7-day interval. Acute infection per se failed to produce overt cytopathology. However, exposure of infected cells to TT resulted in a rapid loss of cell viability, an increase in viral p24 expression, and a decline in T-cell blastogenesis. To determine whether HIV infection of antigen presenting cells (APC) could impact on T-cell activation, virus infected APC were utilized to present TT to responsive CD4+ cells. Use of infected APC produced effects similar to antigen stimulation of infected T-cells. These results suggest that the conditions of antigen presentation during T-cell activation may provide an excellent opportunity for virus transmission which may produce maximal immune dysfunction. However, preincubating antigen specific T-cells with the virostatic agent 3'-azido-3'-deoxythymidine (AZT) could prevent most of these effects.