Peripheral blood mononuclear cell parameters were examined in 17 adult patients with primary herpes simplex virus-1 (HSV-1) infection. Two-color flow cytometry revealed an increase in HLA-DR+ T cell and Leu8+ T cell subsets, and a decrease in CD57+CD16+ subset in the patients. In the symptomatic phase of HSV-1 infection, serum interferon gamma (IFN-gamma) level increased in many patients, and the mean serum level in the patients (0.26 +/- 0.12 U/ml) was significantly higher than the mean control level (0.14 +/- 0.06 U/ml). Soluble intercellular adhesion molecule-1 (sICAM-1) in patients' serum also was increased to a mean level of 398 +/- 130 ng/ml at the first visit. Both the IFN-gamma and sICAM-1 levels fell to near the control levels after the disappearance of oral inflammation. Natural killer (NK) activity was at first increased (mean 46.1 +/- 17.9%), and later decreased to the control level (mean 38.4 +/- 10.6%). In contrast, lymphokine activated killer (LAK) activity at the first visit (mean 53.2 +/- 15.7%) was significantly lower than the control level (mean 69.5 +/- 10.3%). PHA- or ConA-stimulated lymphocytes from the patients incorporated less thymidine than control lymphocytes. These reduced lymphocyte reactivities recovered to the control levels after the disappearance of the acute infection. These results indicate some of the characteristics of lymphocyte pathophysiology in primary HSV-1 infection.