Previous studies have suggested that transmission of measles virus from the opposite sex increases the severity of infection; however, the role of gender in the transmission of other infections has not been examined. Multiple polio cases within a family usually occur simultaneously, and are therefore likely to be secondary to a common subclinical index case. The few clinical polio cases that appear much later than any other clinical case are likely to be tertiary cases. If cross-sex transmission increases the severity of infection then multiple polio cases would tend to affect the same sex, i.e. the opposite sex to that of the subclinical index case. In order to assess this phenomenon we identified 6345 records of individuals hospitalized with poliomyelitis in Copenhagen between 1919 and 1953. The severity and gender of suspected secondary and tertiary cases were analysed among all multiple household cases. Overall, 70% of the 133 sibling pairs having polio simultaneously were same-sex pairs, which differed significantly from the expected 52% (Χ² = 9.1; p < 0.01). Tertiary cases with exposure to the opposite sex were more likely to be paralytic than cases with exposure to the same sex [relative risk (RR) = 2.86 (95% confidence interval 1.08-7.58)]. In families with adult polio cases, possible tertiary cases were more common among fathers (7/24) than among mothers (1/35) [RR = 10.21 (1.34-77.72)]. We examined whether the excess of male polio cases was more pronounced in small families where the mother would play a relatively larger role in disease transmission and found that the male:female excess decreased with increasing birth order (p = 0.02) and family size (p = 0.09). The strong tendency towards same-sex pairs in 2-case families suggests that gender plays an important role in the severity of polio infection. Cross-sex transmission may increase the severity of polio and mothers may contribute to the higher prevalence of polio cases among boys.