We examined the effects of all-trans retinoic acid (RA) on the insulin-induced cell growth, cell cycle progression and cyclin D1 gene expression in breast cancer cells. RA exerted a dose-dependent growth inhibition on insulin-induced proliferation in T47D and MCF-7 hormone-dependent cell lines, whereas MDA-MB231 hormone-independent cells were not affected. The RA antagonism of insulin growth effect was associated with an inhibition of cell cycle progression and a suppression of insulin-induced cyclin D1 mRNA. The effect of RA on cyclin D1 mRNA was dose-dependent and was observed within 5 h of treatment when insulin response was maximal.