This study was aimed at the question of whether or not the antidepressant zimelidine, which is an amphiphilic cationic compound, can induce generalized lipidosis in animals. Rats were chronically treated with high oral doses (80 mg/kg) of the drug, and several organs were examined by light and electron microscopy. Lipidosis-like cellular alterations of considerable degrees were observed in lung, adrenal cortex and lymphatic tissue. Only mild lysosomal alterations were found in hepatocytes, adrenal medulla, retinal pigment epithelium and in peripheral and central nerve cell perikarya. The results show that zimelidine induces generalized lipidosis in rats although of mild degree when compared with some other amphiphilic cationic drugs.