The present study investigated the influence of androgens in potassium homeostasis both under normal conditions and when potassium balance was affected by the mild diuretic amiloride. Our results indicate the existence of a clear sexual dimorphism in renal and plasma potassium content in CD1 mice, adult males having a higher plasma potassium concentration than females or 40-day-old male mice (4.6 ± 1.0 vs. 3.9 ± 0.9 mEq/l). Plasma K<sup>+</sup> concentration was increased by testosterone treatment and decreased after orchiectomy, while the opposite occurred in the case of renal potassium concentration. Amiloride was well tolerated by CD1 female mice, but induced severe hyperkalemia in male mice, where it was also associated with a high rate of mortality. Testosterone treatment increased the toxicity of the diuretic in both CD1 female and male mice. Histopathological analysis of kidneys from CD1 male mice treated with amiloride revealed alterations at the proximal and distal tubule level. These results strongly suggest that androgens may produce adverse effects in renal function.