The aim of the present work was to study the possible association of some class I, II MHC gene products with variations in the clinico-pathological outcome of human schistosomiasis mansoni as well as with the variability in immune responsiveness. The study was carried out on 47 patients with schistosomiasis mansoni and 20 healthy volunteers served as control group for the immunological parameters and 200 subjects for the genetic studies. The following were determined: class I, II HLA typing, serum IgG, IgM, C3c, immediate intradermal test and passive haemagglutination using S mansoni worm antigen, T lymphocyte subsets, delayed intradermal test and leukocyte migration inhibition using phytohaemagglutinin (PHA) and soluble egg antigen (SEA) of S mansoni. A statistically significant association was found between HLA-B5 and DR3 and with the occurrence of hepatosplenic disease; this phenotype also correlated with changes in T lymphocyte subsets and high immune reactivity, both humoral and cell mediated. HLA-DQI was also associated with failure to develop hepatosplenic disease. The present study consolidates also the view of the important role of host immune reactivity in the clinical outcome of schistosomiasis mansoni and demonstrates the contribution of the genetic impact on both clinical and immunological heterogeneity of the disease.