Immunological studies on 12 patients with culture-proven frequently recurrent herpes simplex genitalis were performed. All the patients were evaluated at three time intervals, initially without lesions and/or within 24 hr of lesion onset (acute illness); Days 5-7 from onset and after healing (convalescence); and between recurrences (quiescence). During the first 24 hr of lesions there was a decreased number of helper (CD4+) and an increased number of suppressor/cytotoxic (CD8+) cells with a resultant decrease in the CD4 CD8 ratio. An increased proportion of CD8+ cells coexpressing the CD11 marker (suppressor cells) was noted and correlated with a low proliferative response to HSV-2 antigens. Both the NK cells (CD16+) and the NK cell activity versus HSV-2-infected targets and the K562 cell line were decreased. Five to seven days after onset the number of CD8+ cells remained increased, although the expression of CD11 marker was decreased, indicating that the majority of CD8+ cells were cytotoxic (i.e., CD8+CD11-). At this time, the lymphoproliferative response to HSV-2 antigens and NK cell activity increased, correlating both with the number of CD16+ cells and with the expression of HLA-DR on this subset. In the interval between two recurrences, no significant alteration in any of the above immunological parameters was observed. © 1989.