Streptozotocin (STZ)-diabetic rats regularly retained sodium (Na+), and tended to retain potassium (K+) as well, in response to insulin. Diabetic patients have also been reported to exhibit antinatriuresis and antikaliuresis early in the course of insulin therapy. Insulin-related Na+ retention can occur without a marked reduction in blood glucose level and does not appear to be attributable to preexisting Na+ depletion, mineralocorticoid effect, or suppression of glucosuria. The decrease in urinary Na+ excretion (UNaV) in the rats incident to insulin administration was appreciably greater than the decrease in chloride (Cl-) or water excretion. The significance of this observation is uncertain. It may be, in part, a consequence of the nephrotoxicity of STZ. Insulin-related Na+ retention may be closely related pathogenetically to the Na+ retention of refeeding and may reflect a direct renal action of insulin or, less likely, an alteration of renal tubular metabolism in response to insulin-mediated changes in sytemic metabolism.