To investigate whether mineralocorticoids affect the intrinsic capacity of the proximal tubule to absorb sodium and fluid, rabbits were chronically treated a number of ways to systematically vary plasma concentrations of mineralocorticoid hormones. The rate of fluid absorption and tubule dimensions were measured in superficial S2 segments from these rabbits. Chronic administration of deoxycorticosterone acetate (DOCA) was associated with a 67% increase in fluid absorption and a 29% increase in cell volume per unit tubule length. However, neither adrenalectomy nor low sodium diet significantly affected either fluid absorption or cell volume. Furthermore, marked dietary sodium restriction prevented the response to DOCA. We conclude that the DOCA-induced increases in fluid absorption and cell volume do not result from a direct stimulation of the proximal tubular cells by the steroid but more likely are responses to systemic effects of DOCA administration that are dependent on the level of sodium intake. Thus, we find no evidence for a direct mineralocorticoid stimulation of sodium and fluid transport by the S2 portion of the proximal tubule.