A purified IgG2a monoclonal antibody with a neutralizing titer of 10(4) and specificity for gD was evaluated for its therapeutic potential in a murine ocular infection model. BALB/c mice, infected on the scarified cornea with 10 times the HSV-1 strain RE concentration needed to produce severe and persistent stromal opacity, were given a single inoculation of antibody intraperitoneally 24 hours later. The animals were then followed for corneal disease development. Antibody, at concentrations as low as 10 micrograms per mouse, was strikingly effective at preventing corneal opacity. Furthermore, the corneas, once clear, remained clear whereas the controls developed +3 to +5 stromal disease which was still present 60 days post-infection. Animals that had been treated and recovered from infection were resistant to subsequent HSV-1 challenge on the opposite cornea. These results demonstrate the therapeutic potential of systemically administered microgram quantities of anti-gD antibody.