To determine whether intravenous acyclovir treatment for a first episode of genital herpes could prevent or reduce subsequent recurrences, we combined and analyzed the results of two independently conducted, randomized, double-blind, placebo-controlled studies. Sixty-one patients were enrolled in the two trials; 30 received the drug, and 31 received placebo. At entry the demographic, epidemiologic, and clinical features of acyclovir- and placebo-treated patients from the two centers showed no significant differences. The median time to the first recurrence and the frequency of recurrences showed no significant differences when acyclovir and placebo recipients infected with either herpes simplex virus type 1 (HSV-1) or herpes simplex virus type 2 (HSV-2) were compared. However, irrespective of treatment, the median time to the first recurrence was significantly longer (293 days vs. 69 days; P less than .02) and the frequency of recurrence significantly less (0.11 recurrences per month vs. 0.43 recurrences per month; P less than .01) among patients with HSV-1 infection as compared with those who had HSV-2. It is concluded that in patients with first-attack genital herpes, the type of HSV is the most important determinant of subsequent recurrences and that intravenous acyclovir has little effect on subsequent recurrences.