The effects of erythromycin estolate, a well known hepatotoxic macrolide antibiotic, on isolated rat hepatocyte viability and on subcellular Ca2+ transport have been investigated. Erythromycin estolate (0.5 mM), but not erythromycin base and erythromycin ethylsuccinate, induced 100% cell death after 60 min incubation, and caused maximal inhibition of mitochondrial and microsomal Ca2+ sequestration activities at 0.1 mM concentration. Sodium lauryl sulphate, which is the surfactant moiety of the erythromycin estolate molecule, caused effects similar to those exhibited by erythromycin estolate. Disorders of the intracellular calcium homeostasis seem to play a role in the lauryl sulphate-mediated hepatotoxic action of erythromycin estolate.