Schistosomiasis mansoni is basically an immunological disease due to the pathophysiological sequelae of a cell-mediated granulomatous inflammatory reaction around the eggs of the parasite trapped in the host tissues. An immunoregulatory response has been observed in chronic Schistosoma mansoni infections in experimental animals, and possibly in man, which results in modulation of the granulomatous inflammation and amelioration of the disease state. This paper will briefly review the immunopathogenesis of schistosomiasis mansoni, and then consider the observations on modulation and its mechanism. Evidence that such immunoregulatory phenomena are occurring in animal models of the other major human schistosome infections—S. japonicum and S. haematobium—will be presented, as will observations on modulation in man, its possible mechanisms and its implications. Immunopathogenesis The major clinical manifestations of infection with the three principal species of human schistosomes are essentially related to obstruction to blood or urine flow due to inflammatory and fibrotic responses to products of the helminth.