A randomised, placebo-controlled, multi-centre trial of intracellular subunit herpes simplex virus (HSV) type 1 vaccine NFU.Ac.HSV-1(S^–)MRC (Skinner vaccine) was conducted at three medical centres in the United States. Subjects with documented herpes genitalis of at least 1-year duration and a history of six or more genital HSV recurrences in the 12 months prior to study entry were randomised to receive vaccine or placebo at 0, 1 and 2 months. Vaccination induced significant neutralising, enzyme-linked immunosorbent assay and lymphocyte transformation response to HSV-1 antigen. The frequency of recurrences was reduced in the vaccinated female patients at both 3 and 6 months following vaccination with an overall reduction in patients of both sexes which did not reach statistical significance. Recurrence severity was reduced as measured by decreased number of lesions and associated symptoms per recurrence (P = 0.04). The data suggest that clinical manifestations of latent HSV genital infection may be modified by therapeutic immunisation.