127 patients with suspected herpes simplex encephalitis (HSE) were entered in a prospective randomised study of acyclovir 10 mg/kg 8-hourly versus vidarabine 15 mg/kg daily for 10 days. The patients were consecutive and nearly all Swedish cases of HSE were included; they were treated in six university infectious diseases departments. The diagnosis of HSE was verified by brain biopsy and/or antibody responses in serum and cerebrospinal fluid. Of 53 confirmed cases of HSE (corresponding to 2 X 3 cases per million inhabitants per year in Sweden), 51 (27 acyclovir, 24 vidarabine) were evaluable for analysis of efficacy. The mortality was 19% in the acyclovir-treated group versus 50% in the vidarabine group (p = 0.04). At 6 months of observation 15 (56%) of 27 acyclovir-treated patients had returned to normal life compared with 3 (13%) of 24 vidarabine-treated patients (p = 0.002); and the numbers who died or had severe sequelae were 9 (33%) and 19 (76%), respectively (p = 0.005). No important or new adverse events were recognised.