Intragastric administration of live herpes simplex virus type 1 (HSV-1) was assessed for the induction of humoral immune responses and for protection against ocular and cutaneous challenge with virus. Mice showed no clinical abnormalities following intragastric inoculation with three different strains of virus (Miyama +GC, SC16, and P2C6, a thymidine kinase-defective mutant). Replication of virus was not detected in the oesophagus, superior cervical ganglia or coeliac ganglia of such animals and latent infection was not detected in these ganglia at later times after inoculation. Induction of a mucosal immune response was indicated by the presence of antibody (mainly IgG or IgA)-secreting cells in Peyer's patches. Intragastric immunization gave protection to some extent against ocular challenge and to a greater extent against cutaneous challenge with HSV-1. Following the latter challenge, particularly after intragastric immunization with strains SC16 and Miyama, the establishment of latency was almost completely prevented.