To document the frequency of genital herpes recurrences in men and women with histories of recurrent genital herpes during 1 year of continuous, suppressive therapy with valacyclovir hydrochloride (HCl). In an open-label clinical trial conducted at 11 centers, 127 subjects (46 women and 81 men) with histories of recurrent genital herpes (at least 6 recurrences per year) were treated with valacyclovir HCl (500 mg once daily), and their clinical status was followed up for 1 year. Genital herpes recurrences were documented in diaries, and quarterly clinic visits were made for evaluating lesion recurrences and drug safety. In cases of recurrence, subjects self-treated with valacyclovir HCl 500 mg twice daily for 5 days, then resumed once-daily treatment. After the first 3 months of suppressive therapy, 81% of subjects were free of recurrence. Recurrence-free rates remained undiminished during the second, third, and fourth quarters (84%, 84%, and 91%, respectively) and were similar for men and women. Thirty of 46 women (65%) and 56 of 81 men (69%) remained recurrence free during the study and therapy was well tolerated. Adverse events were mild, infrequent, and not considered related to the study drug. Valacyclovir HCl was highly effective and well tolerated as continuous suppressive therapy in men and women with recurrent genital herpes. Potential benefits of the once-daily regimen of valacyclovir HCl include improved patient compliance.