Adherent, trypsin-resistant, peritoneal cells from mice with chronic schistosomiasis mansoni, and from control mice, were cultivated in vitro up to 20 days. Fibroblasts regularly appeared, about 6 days after seeding, in cultures ofthe manyfold more numerous cells from infected mice, concomitantly with a dramatic increase, detected by autoradiography, in the percentage of DNA-replicating cells of the monocyte-macrophage lineage. Peritoneal cells from healthy and from infected mice were fractionated on discontinuous Percoll gradients. Eight cell subsets were harvested in both cases, quantitated, and studied by electron microscopy. Two fractions (2 and 3: 1.041 < densities < 1.060 g/ml) from infected mice were greatly enriched in monoblasts and promonocytes. The cells of the different subsets were seeded separately, trypsin-treated and cultivated in vitro. Cultures of cell fractions 2 and 3 from infected mice contained the majority of the DNA-synthesizing cells and gave regularly rise to fibroblasts. Cultures of the different fractions were used for sequential morphological observations (2-11 days) at the electron microscope level. Early cultures were also used for the ultrastructural detection of the Mac-1 (CD 18/CD11b) surface antigen by gold immunocytochemistry. A few fibroblasts were rarely observed in cultures of fractions 2 and 3 from control mice, while cells with ultrastructural features of myofibroblasts were regularly observed in cultures of the same fractions harvested from mice with chronic schistosomiasis. Fractions 2and 3 from infected mice contained a large number of Mac-1 positive monoblasts. The correlations between the presence of monoblasts, DNA replication in cells ofthe monocyte-macrophage lineage and the appearance of myofibroblasts in culturesof the same fractions derived from infected mice are discussed.