In patients with the hepatosplenic form of schistosomiasis, portal hypertension and collateral circulation develop, thus diverting the schistosomes and their eggs from the portal to the pulmonary vasculature. In some of these patients chronic cor pulmonale develops. To study the pathogenesis of this latter condition, a histologic search was performed on the sections of the lungs taken from 78 persons with hepatosplenic schistosomiasis. These lungs were then classified into four groups: Group 0—normal lungs (22 cases); Group 1—few scattered periovular granulomata in the alveolar tissue (35 cases); Group 2—numerous periovular granulomata involving the alveolar tissue and the pulmonary arterioles, with absence of vascular hypertensive lesions (seven cases); and Group 3—segmental, chronic obliterative arteritis, with disseminated egg granulomata and diffuse vascular hypertensive changes (14 cases). Chronic cor pulmonale occurred in the cases in groups 2 and 3. The lesions found in the former seemed to precede those lesions found in the latter group. Both groups showed evidence of massive and rather sudden egg embolization to the lungs. Thus, cor pulmonale in schistosomiasis apparently resulted from a massive infection rapidly progressing to portal hypertension with collateral circulation. On the other hand, no evidence was found that pulmonary arteritis could result from a gradual accumulation of egg granulomata in the lungs during prolonged periods, as could have happened in the two first groups of cases.