Objective: To examine whether proviral load is important for transmission between spouses, since we have previously found that the proviral load of HIV-2 predicts the severity of infection. Design: Proviral load was examined in 121 HIV-2-infected adults in a rural area of Guinea-Bissau. For the 68 subjects who had a spouse of known HIV status the risk of the spouse being infected was examined. Methods: Statistical methods for dependent data were used, because several couples were polygamous. Results: Twenty-seven HIV-2-infected men had 52 current wives of whom 17 (33%) were HIV-2-seropositive. Forty-one HIV-2-infected women had 36 current husbands of known HIV serostatus; nine (25%) were HIV-2-positive. In univariate analyses, concordance of female partners of HIV-2-infected men increased with a previous history of prostitution, age of wife, lack of age difference between the spouses, number of previous husbands, number of wives of the man, and the proviral load. The only significant predictor of concordance in multivariate analyses when wives with a history of prostitution were excluded was an age of 45 years or older [odds ratio (OR), 8.68; 95% confidence interval (CI), 2.34-32.22]. This tendency was not explained by the length of current marriage. Although husbands with a high proviral load were more likely to have concordant spouses than those with a low proviral load (< 20 copies/10⁵ CD4 cells), this association was not statistically significant (OR, 2.59; 95% CI, 0.90-7.46). Among spouses of HIV-2-infected women, none of the examined factors, including previous prostitution or proviral load in the woman, predicted whether the husband was HIV-2-infected. Conclusions: Women appear to be more susceptible to HIV-2 infection after 40-45 years of age. The apparent change in susceptibility may be a major reason for the distinctive age pattern of HIV-2 infection observed in West Africa.