Antibodies to herpes simplex virus (HSV) have been demonstrated in cervicovaginal secretions but have not been analyzed for their viral protein targets, prevalence, isotype, or kinetics of development. A method was devised to collect cervical secretions from women with primary genital HSV-2. By Western blot, cervical IgG and IgA responses to HSV-2 proteins VP5, gB, and gD were detected in most patients within 2 weeks of onset and to gC/gE within 3 weeks. Cervical IgM and IgG responses to gG, VP16, and ICP35 developed later and were more variable. Cervical IgM to most proteins appeared within 6-10 days. Cervical IgA and IgG persisted for weeks, but cervical IgM waned. Western blot profiles of serum IgG and cervical IgG to individual HSV-2 proteins were similar; those of serum IgA and cervical IgA differed. These findings suggest a universal, complex immune response to HSV-2 infection in the female genital tract.