The purpose of the present study was to evaluate the efficacy and safety of parenteral administration of interferon alpha-2α in the treatment of recurrent herpes genitalis. A total of 97 patients (66 males, 31 females, mean age 34.86 ± 16.74 years), who had at least five recurrences of genital herpes during the previous 12 months, participated in a prospective open study on the effects of treatment with interferon alpha-2α (Roferon-A; Roche). The patients were treated with interferon alpha-2α (3 × 106 IU) by subcutaneous injection, three times weekly for 4 weeks, and the same schedule was repeated after 3 and 6 months. All patients were asymptomatic at the start of the study. After initiation of treatment, all patients reported to the clinic every 3 months for 2 years (the males were submitted to peoscopy and the females to Pap test and colposcopy) at the time of their recurrences. Comparison was made of the number of recurrences, duration of lesions, duration and severity of pain, and itching and burning. Prophylactic administration of interferon alpha-2α prevented recurrences of genital herpes virus infection in 51 patients (20 males and 31 females). Interferon administration shortened the healing time from 8.5 days before treatment to 2.5 days after treatment (p < 0.001). There was a significant reduction in the number of recurrences during the study period, from 7.46 before treatment to 2.64 after treatment (p < 0.001). On the basis of the overall efficacy and adverse effects, this regimen may be of value in the routine treatment of recurrent herpes.