The antibody response to herpes simplex virus (HSV) is complex and involves antibody to at least 33 virus-induced polypeptides. Serum IgG contains four isotypes in mice and it is known that the isotypes differ in their biological functions and that individual antigenic proteins may preferentially elicit restricted isotype responses. We therefore examined the anti-polypeptide isotypes induced in immune mouse serum. By ELISA, we found that the total serum virus-specific antibody activity was 51% IgG1, 39% IgG2a, 11% IgG2b and 1% IgG3 in immune ICR strain mice and 51%, 45%, 4% and 0.4% respectively in strain BALB/c mouse immune serum. These proportions are significantly different from those reported for other virus infections. Sepharose-Protein A affinity-purified isotypes were also studied and showed IgG1 greater than IgG2a greater than or equal to IgG2b much greater than IgG3 activity per microgram of isotype, indicating that competition between isotypes present in high concentrations did not significantly alter the results. Immunoblotting studies of the purified isotypes showed that the major immunogenic HSV-1 proteins (VP155, gC, gB, pgB, gD and nucleocapsid proteins 42K and 44K) induced all isotypes. However, the isotype responses were not uniform among the glycoproteins and some other proteins. In addition neutralization assays of the purified isotypes indicated that IgG2a and IgG2b had significantly greater neutralizing capacity than IgG1, suggesting that less of the IgG1 was directed against neutralizing virion epitopes. These data are discussed with respect to the biological implications in host defence.