Peripheral blood mononuclear cells obtained from 4- to 6-month-old-calves were inoculated in vitro with bovine herpesvirus-1, parainfluenza-3, or bovine virus diarrhea viruses. No increase in infectious virus progeny was observed; however, the viruses were detected in the cells for at least 96 h post-infection without any significant reduction in cell viability. The three viruses, either alone or in combination, suppressed phytohemagglutinin-induced proliferation of the mononuclear cells. The greatest suppression was observed in cultures inoculated with bovine virus diarrhea virus. Addition of isoprinosine partially restored this viral-induced suppression of proliferative response, and the efficiency of reversal was greater in bovine virus diarrhea virus-infected cells. Interleukin-2 activity was higher in cultures of virus-infected mononuclear cells than in cultures of non-infected cells.