The standard course of antiviral therapy for recurrent genital herpes requires administration of multiple doses of medication for 5 days. To assess the efficacy of a shorter course of antiviral therapy, patients with recurrent genital herpes simplex virus type 2 (HSV-2) infection were enrolled in a randomized, double-blind, placebo-controlled study of acyclovir (800 mg given by mouth 3 times per day [t.i.d.]) for 2 days. Of 131 people enrolled in the study, 84 (51 women and 33 men) were observed for >/=1 recurrence and 65 were observed for 2 recurrences, for which the patient was administered the same study drug (acyclovir or placebo). Acyclovir therapy (800 mg given by mouth t.i.d. for 2 days) significantly reduced the duration of lesions (median for acyclovir versus placebo, 4 days versus 6 days; P=.001), episode (4 days versus 6 days; P<.001), and viral shedding (25 hours versus 58.5 hours; P=.04), and it increased the proportion of aborted episodes (P=.029). A 2-day course of acyclovir is a convenient alternative for treatment of recurrent genital herpes.