Major histocompatibility class II alleles of 351 persons living in an area endemic for Schistosoma mansoni in northeastern Brazil were characterized at three loci (DRBl, DQAl, and DQBl). Contingency analyses were used to compare allele frequencieswitfihigh egg excretion, proliferative response to schistosome soluble egg antigens (SEA), and occurrence of severe, biopsy-confirmed hepatosplenic disease. There were no associations of HLA-DR or DQ with egg excretion. Patients positive for DRBl*01, DQAl*0101, or DQBl*0501 were less likely to respond to SEA than was the overall study population. However, using stringent Bonferroni correction (multiplying P values by the number of alleles tested; P × 35), none of these associations with SEA responsiveness remained significant. Hepatosplenic disease was less likely in patients positive for DRBI*11 and was more likely in patients positive for DRBl*07 or DQBl*0201. However, only the DQBl*0201 association remained significant (odds ratio = 3.72; P < .005) following Bonferroni correction.