Sphingolipid metabolites are important regulators of cell growth and differentiation. Recent studies have suggested that sphingosine-1-phosphate, a biologically active sphingolipid metabolite, acts as a crucial messenger in apoptosis. In the present work, we examined the expression levels of the members of the bcl-2-related gene family to determine their roles in sphingosine-1-phosphate-induced apoptosis in human hepatoma cells. Our results indicate that sphinogosine-1-phosphate-induced apoptosis is associated with enhanced expression of Bax protein. Moreover, the regulation of bax gene expression by sphingosine-1-phosphate is independent of the p53 tumor suppressor. (C) 1996 Academic Press, Inc.