Many viruses enter lympho-reticular cells during pathogenesis and thereby induce immunosuppression, which is of practical importance in that it may be related to overall virulence. Immunosuppression may result from a selective infection, as viruses often show an affinity for different lymphocyte subpopulations: Epstein-Barr virus, for example, infects only a small percentage of B cells. We reported previously that herpes simplex virus (HSV) type 1 suppressed the induction of an antibody response to diphtheria toxoid in cultures of human tonsil cells, and that this seemed to result from the infection of a small percentage of T lymphocytes. However, as fully infectious virus was used in these experiments, it had probably spread from cell to cell in the course of the culture, so complicating the interpretation of the results. Accordingly, we have now reinvestigated the mechanism of immunosuppression using temperature-sensitivity (ts) mutants which fail to complete their growth cycle in the conditions selected for antibody synthesis. In this study, mutants tsB, tsD and tsF, derived from HSV type 1 strain 17, and ts 9, derived from HSV type 2 HG 52, were used. The results suggest that the immunosuppression is due to the selective infection by the viruses of helper T cells.