Schistosoma mansoni-infected mice tend to present with either one of two different hepatic pathological patterns during chronic infection: periportal fibrosis (PF) with portal concentration of periovular granulomas and fibrosis or isolated granulomas (IG), with scattered periovular granulomas within the liver. These are models for the two clinical presentations of schistosomiasis, the severe hepatosplenic and the mild intestinal forms. In the present work, we examined the relationship between the development of these histopathological aspects and immunological markers in S. mansoni-infected mice. Although BALB/c mice with PF and IG had similar egg numbers in the liver, PF mice had higher liver collagen contents than mice with IG. Cultured spleen cells from mice with PF and IG had similar proliferation 20 and 40 weeks after S. mansoni infection upon stimulation with parasite egg antigen (SEA) or mitogen (Con A). Production of IL-4 upon SEA stimulation was higher in cell cultures from mice with PF, whereas IL-5 and IFN-gamma levels were not statistically different between PF and IG groups. Mice with IG had similar serum concentrations of total IgE and anti-SEA IgG1, IgG2a, IgG2b and IgG3 compared to sera from PF mice. Levels of IgG1 and IgG2a antibodies were the highest and the lowest detected, respectively. In conclusion, isogenic BALB/c mice infected with S. mansoni that develop periportal fibrosis or isolated granulomas have similar immunological patterns despite the two pathologic forms of schistosomal liver fibrosis.