Up to now, only glucocorticoids were thought to act on the renal proximal Na+/H+ exchanger. Using fluorimetric techniques we studied the kinetics of Na+/H+ exchange in brush border vesicles from ADX rats treated with increasing doses of corticosterone (B) and 18-hydroxycorticosterone (18OHB). Significant linear correlations were obtained when the Vmax of each treatment were plotted against log doses. 18OHB exhibits a slightly higher sensitivity than B and log-dose responses were steeper for 18OHB than for B treated rats. Differences between both treatments were highly significant at the 4.8 μg/100 g level, corresponding to the physiological blood level of 18OHB. Physiological doses of both steroids elicited equal Na+/H+ exchange-responses. 18OHB is not a glucocorticoid since even 88μg/100g did not promote hepatic glycogen deposition while the same dose of B increases glycogen deposits 3.5-fold. These results demonstrate the importance of the Na+/H+ exchanger as a mediator between corticoid action and H+ transport and that of the non-glucocorticoid 18OHB in this process.