Endemic Kaposi's sarcoma (KS) in Africa has been attributed to a geographically-determined environmental factor. Endemic KS, a chronic nodular condition predominantly affecting the feet and legs, is believed to arise in the lymphatic endothelium and is associated with chronic lymphoedema. As such, KS bears a resemblance to podoconiosis (non-filarial elephantiasis). The prevalence of both conditions in highland areas close to volcanoes suggests a shared pathogenetic relationship to exposure to volcanic soils. The lymphatics and lymph nodes of patients with podoconiosis contain particulate alumino-silicates in macrophages consistent with the theory that ultrafine clay minerals are absorbed through the feet. The resulting chronic lymphatic irritation, inflammation, and collagenosis causes obstruction and lymphoedema. The geographical proximity of endemic KS to areas containing volcanic clay minerals, its lympho-endothelial origin, predilection for the feet and legs, and its prevalence among rural peasants and cultivators, suggest a common aetiology. Other features point to the participation of a low-grade, possibly sexually-transmitted, infective agent that becomes more pathogenic in the presence of immunosuppression. Damage to the dermal lymphatics of the feet and legs by absorbed clays could impair local immunity to such an agent. Endemic KS would then occur in exposed individuals who harbour the KS infective agent and are susceptible to the KS phenotype (males).