Opposite gender transmission may increase the severity of certain infections. If infections transmitted from mother to son were more severe than from mother to daughter this might explain severe diseases among boys, particularly in small families with few individuals contributing to transmission. Among children from Guinea-Bissau, we tested whether mothers with recent respiratory syncytial virus exposure (positive IgM and IgA antibody responses) were more likely to have male than female children with respiratory syncytial virus antigen positive acute lower respiratory tract infection. Children with acute lower respiratory tract infection were identified at a paediatric clinic (n = 348), a health centre (n = 270), and in a community morbidity survey (n = 525), 14.2% (162/1143) having respiratory syncytial virus antigen. An equal number of boys and girls had acute lower respiratory tract infection, but boys were more likely to have respiratory syncytial virus detected (prevalence ratio = 1.36 (1.01-1.81)), this difference being particularly marked in the rainy season. With recent respiratory syncytial virus exposure of mother, boys were twice as likely to have respiratory syncytial virus detected (prevalence ratio = 2.04 (1.18-3.53)), the difference being marked in the rainy season. There was no gender difference in respiratory syncytial virus infection among children of RSV negative mothers. We conclude that mothers may transmit respiratory syncytial virus more easily or severely to sons.