Interleukin-6 (IL-6) has been suggested as an autocrine growth factor of human renal cell carcinomas. Since steroids are known to inhibit IL-6 gene expression, we investigated their effects on the growth of renal cell carcinoma. Dexamethasone inhibited proliferation of 2 of 4 renal cell carcinoma cell lines in a dose-dependent manner. In one of these 2 cell lines, IL-6 gene expression was also inhibited, but not in the other. The inhibitory effect of dexamethasone on cell proliferation was not reversed by the exogenous IL-6. In 1 of the 2 remaining cell lines, the inhibition of IL-6 gene expression was observed, although there was no inhibition of cell proliferation. Thus, inhibition of growth by dexamethasone did not correlate with an inhibitory action of dexamethasone on IL-6 mRNA expression. Progesterone inhibited the growth of 1 cell line without concomitant inhibition of IL-6 gene expression. Expression of IL-6 receptor mRNA was not altered. A dose-dependent increase in mRNA expression of gp130, the transducer of IL-6 signal, was induced by dexamethasone and progesterone in 2 and 1 of the 4 cell lines, respectively. These data suggest that, in some renal cell carcinomas, steroids may inhibit cell proliferation by a mechanism independent of their effects on mRNA expression of IL-6 and IL-6 receptors. Dexamethasone may be useful, not only for palliation of paraneoplastic syndrome caused by overproduction of IL-6, but also for inhibition of growth of renal cell carcinomas.