In human schistosomiasis, the concentrations of the chemokine macrophage inflammatory protein 1␣ (MIP-1␣/CCL3) is greater in the plasma of patients with clinical hepatosplenic disease. The objective of the present study was to confirm the ability of CCL3 to detect severe disease in patients classified by ultrasonography (US) and to evaluate the potential role of CCL3 in Schistosoma mansoni-infected mice. CCL3 was measured by enzyme-linked immunosorbent assay in the plasma of S. mansoni-infected patients. CCL3-deficient mice were infected with 25 cercariae, and various inflammatory and infectious indices were evaluated. The concentration of CCL3 was higher in the plasma of S. mansoni-infected than noninfected patients. Moreover, CCL3 was greater in those with US-defined hepatosplenic than with the intestinal form of the disease. In CCL3-deficient mice, the size of the granuloma and the liver eosinophil peroxidase activity and collagen content were diminished compared to wild-type mice. In CCL3-deficient mice, the worm burden after 14 weeks of infection, but not after 9 weeks, was consistently smaller. The in vitro response of mesenteric lymph node cells to antigen stimulation was characterized by lower levels of interleukin-4 (IL-4) and IL-10. CCL3 is a marker of disease severity in infected humans, and experimental studies in mice suggest that CCL3 may be a causative factor in the development of severe schistosomiasis.Schistosomiasis is one of the most prevalent helminth diseases in the world and is caused by blood flukes of the Schistosoma genus (36). In infected individuals, the granulomatous inflammation in response to egg deposition in the liver in the case of Schistosoma mansoni is the major pathological finding and accounts for most of the clinical symptoms. Worm oviposition at 5 to 6 weeks poses a strong Th2 bias in the immune response against infection (6) while also inhibiting the Th1 component (12,42). Nonetheless, the granulomatous response that is maximal during the first few weeks after initial oviposition is also subjected to immunomodulation. Apart from interleukin-10 (IL-10) (29), other factors may also be involved in this process. For example, recent literature suggests that, in animal models, the granulomatous response that occurs at chronic time points is dependent on the soluble form of the IL-13 receptor ␣2 (27). In patients, failure in modulating the response might lead to the development severe schistosomiasis later in life (15). Indeed, a direct consequence of the persistence of an exacerbated immune response appears to be the development of large granulomatous reactions associated with intense collagen deposition (20) and the development of hepatosplenic schistosomiasis. Therefore, there is much scientific interest in the understanding of the mechanisms and inflammatory mediators underlying egg-induced granulomatous response, with the ultimate goal of proposing strategies to modulate fibrosis. It is known, however, that prevention of granuloma formation may be dangerous, since lethality ...