Human recombinant interleukin-2 (rIL-2) modifies infection with herpes simplex virus type 2 (HSV-2) in normal guinea pigs. Animals were injected sc with rIL-2 twice a day, beginning 24 hr before infection and continuing for three subsequent days. Guinea pigs were assigned to five different regimens in which rIL-2 was administered daily at dosages from 8 X 10(3) U/kg to 8 X 10(5) U/kg. After intravaginal inoculation with HSV-2, 83% of 24 control animals developed apparent genital herpes, and 5% had asymptomatic viral shedding. Animals receiving 4 X 10(4) U or 2 X 10(5) U or rIL-2/kg showed a significantly lower rate of infection (P less than .001 by chi 2) and a lower number of lesions and more rapid healing than did the infected animals in the control (untreated) group. The mortality in the untreated group (28%) was higher than in the animals in the 2 X 10(5) U/kg treatment group (7%). No difference was observed between the control, the 8 X 10(3) U/kg, and the 8 X 10(5) U/kg treatment groups with respect to severity of infection or mortality. Animals examined two to four weeks after inoculation had lymphocyte stimulation indices (induced with HSV-2 antigen) greater than 3.5 and titers of antibody between 2.5 log10 and 4.5 log10 by radioimmunoassay. In the disease-free animals, stimulation indexes were less than 2 and antibodies were undetectable. The mean stimulation index was 54 +/- 16 in the diseased control animals and 12 +/- 7 (P less than .05) in the 2 X 10(5) U/kg treatment group.(ABSTRACT TRUNCATED AT 250 WORDS)