Low levels of dexamethasone and related gluco-corticoid hormones suppress the expression of globin genes during the DMSO-induced differentiation of Friend leukemia cells. In this response, the glucocorticoids appear to act at both the transcriptional and post-transcriptional levels in that 10-8 M dexamethasone prevents the accumulation of both globin mRNA and globin protein, whereas 10-9 M dexamethasone allows the accumulation of normal levels of hybridizable globin mRNA but prevents the accumulation of globin protein. This suppressive action of dexamethasone is more effective with DMSO as the inducer of globin gene expression than with hemin as the inducer. In contrast to the situation with glucocorticoids, certain sex steroids (etiocholanolone, testosterone and estradiol) facilitate the expression of globin genes in DMSO-treated Friend leukemia cells. The modulation of globin gene expression by steroid hormones is achieved in DMSO-treated cells without altering the growth and morphological changes which characteristically attend the differentiation of these cells.