Sixty-three episodes of genital herpetic infection in 55 men and 45 episodes in 42 women were randomly assigned to topical treatment with 3% adenine arabinoside, topical treatment with placebo ointment, or no therapy. In addition, 10 episodes in women who were not randomly assigned to therapy were evaluated and followed. Clinical evaluation and viral cultures were done on day 3, day 8, and weekly thereafter until the lesions had healed. The natural clinical course of genital herpetic infection was defined in patients given placebo or no therapy. Patients with a history of previous genital herpetic infection had significantly less pain, few lesions, and shorter duration of illness and viral shedding than patients who had no history of previous genital infection with Herpesvirus. An unexpected finding was that 87% of women experiencing their first episode of genital herpetic infection had cervical cultures positive for Herpesvirus hominis, whereas only 4% of women with recurrent herpetic infection had a positive cervical culture. Treatment with 3% adenine arabinoside did not influence the course of either primary or recurrent genital infection with Herpesvirus.