In this work, the cytotoxic effects of some spirostane derivatives were examined in cultured hepatocytes and V79 fibroblasts using different viability assays. The derivatives were obtained by modifying the A and B rings of diosgenin. Diosgenin and its derivatives were more toxic in V79 fibroblasts (IC50 40-300 microM) than in hepatocytes (IC50 280-1000 microM). Inhibition of cytochrome P450IIIA in cultured hepatocytes by incubation with 1 mM cimetidine did not alter the toxicity of these compounds in these cells. These observations suggest that other pathways of detoxification may be involved in hepatocytes. In conclusion, the compounds studied merit investigation for their potential pharmacological and industrial applicability.