To explore how gender and social class affect perceptions of health status among 16-year-old adolescents. Cross-sectional survey. University psychology laboratory. PARTICIPANS: Fifty upper-middle-class and 48 working-class adolescents stratified by gender. The general health perceptions (GHP) scale of the Medical Outcomes Survey 36-Item Short Form Health Survey (SF-36). The other self-reported health status domains and 3 measures of different aspects of psychological well-being were included as covariates in analysis of variance models. Upper-middle-class females reported the lowest and upper-middle-class males the highest GHP (76.7 vs 88.4, P=.003). A multivariate regression model (adjusted R2=0.08) revealed significant gender (P=.03) differences in GHP, but not a social class effect, and an interaction effect between gender and class (P=.01). With addition of psychological well-being covariates (P<.001), gender remained significant (P=.04) and a significant portion of the interaction effect (P=.13) was explained. When the self-reported physical health status scales (P<.001) were added to the model (adjusted R2=0.51), gender remained significant (P=.03) and the interaction effect was partially explained (P=.07). Gender is a crucial factor in understanding the complex relationships between sociostructural inequalities and health differentials. These data suggest that psychological well-being and self-reported physical health status mediate the effects of gender and the gender and social class interaction in explaining variation in GHP. Contrary to the social class gradient hypothesis, upper-middle-class females reported the lowest GHP. These results suggest that the paradigms applicable to early childhood and adulthood may not be appropriate to understand the complex dynamics of adolescence.