Summary In nine patients with oral or genital primary herpes-simplex-virus infection, examined by the indirect immunofluorescence technique, IgG and IgM anti- bodies were both present by the sixth day. Significant titres of IgM persisted for 8 weeks or more. No changes in antibody titre were observed in three patients with clinical recurrences; in only two of five patients with a history of recurrences was IgM detectable, and at low levels. Eight adult patients with herpes-simplex encephalitis (HSE) showed serum IgG and IgM antibody responses similar to those seen in the non-encephalitic primary infections, although in one of the cases the IgM antibody was detected only after sucrose density-gradient fractionation of the serum. Another patient with HSE and a past history of cold sores had a low, unchanging level of IgM antibody in the serum that persisted for about 10 weeks. IgG antibody, but no IgM antibody, was found in the CSF of the patients with HSE. I am greatly indebted to Dr F. 0. MacCallum and Dr A. H. Tomlinson for continued encouragement, help and advice during this study.