Previous studies of measles mortality in West Africa have shown a significantly higher case-fatality rate (CFR) among girls than among boys. This study aimed to find out whether the male/female difference in CFR is related to different risks for boys and girls of being infected as secondary rather than index cases and of transmission from someone of the same or the opposite sex. The study was conducted in Niakhar, a rural area of Senegal (population 24,000). All cases of measles reported between March, 1983, and December, 1986, were investigated to determine source of infection and pattern of transmission. For each case, the closest source of infection was judged the most likely. Death was attributed to measles if it occurred within 6 weeks of the onset of rash. Girls had a higher measles CFR than boys (53 deaths/722 cases [7.3%] vs 45/778 [5.8%]); the relative risk of death was 1.30 (95% confidence interval [CI] 0.89-1.90). Secondary cases infected by a child of the opposite sex had a 2.44 (1.48-4.02) times higher risk of death than did secondary cases infected by a child of the same sex. The risk of cross-sex transmission of infection was significantly greater for female than for male secondary cases (1.26 [1.09-1.47]). When this difference in risk of exposure to infection from the opposite sex was taken into account, the difference in risk of death between girls and boys disappeared (1.06 [0.66-1.69]). Within families, the CFR was higher in huts with 1 boy and 1 girl affected than in huts of either 2 boys or 2 girls affected (relative risk 2.16 [0.99-4.70]). Measles infection contracted from a person of the opposite sex is more severe. Variation in exposure may be an important determinant of sex differences in case fatality.