In a prospective study of factors associated with genital herpes simplex virus (HSV) type 2 transmission in couples in whom 1 partner had clinical genital HSV and the other did not, 11 (19%) of the 57 history-negative partners had HSV-2 antibody by Western blot at entry. In follow-up (mean, 16 months) of 29 HSV-2-seronegative partners, overall 4 (14%) seroconverted compared with 3 (23%) of 13 HSV-1- and -2-seronegative partners and 1 (6%) of 16 HSV-1-seropositive partners. Since all seroconverters were women, the risk of transmission may be higher in HSV-seronegative women. No significant differences were found between HSV-2-seronegative partners and seroconverters regarding duration of relationships, number of partner recurrences, intercourse frequency, or contraceptive method. However, 2 seroconverters were exposed to lesions without barrier contraception. This study suggests that infection is commonly asymptomatic and that although the overall risk of genital HSV transmission in couples is low (10%/year), the risk may be significantly increased in women and in seronegative individuals.