In schistosomiasis endemic areas, antibody isotype responses against Schistosoma mansoni antigens vary with host age, sex and duration or intensity of infection, and are associated with susceptibility or resistance to infection. Identifying the quality and quantity of these responses is important to our understanding of the host-parasite relationship; however, the various host and parasite factors have a strong tendency to confound each other. We investigated the relationships and interactions between age, sex, faecal egg-counts and specific antibody isotype (IgA, IgG1, IgG2, IgG3, IgG4, IgE, IgM) responses to S. mansoni worm (SWA) and egg (SEA) antigens, amongst 380 individuals aged 5-59 from a fishing community from Uganda. This community was characterized by high levels of exposure, and high infection intensities, with higher infection intensities in males than in females. Multivariate anova was conducted with interaction terms between the three categorized explanatory variables. Most anti-SWA responses increased with age, whereas anti-SEA responses tended to decline with age, especially after puberty. IgG1-SWA, IgG4-SWA, IgG4-SEA, IgE-SWA responses increased with egg count, whereas IgG2-SEA decreased with egg count. IgG1-SWA, IgG4-SWA, IgE-SWA and IgG4-SEA responses were independently higher in males, whereas IgG2-SEA responses were independently higher in females. The significant effects of sex on isotype responses to adult worm antigens may be partly because of different levels of cumulative exposure. IgG4-SEA and IgG4-SWA were both strongly correlated with egg count. Patterns of IgE-SWA responses were qualitatively different to IgG4 responses, suggesting independent pathways of regulation.