The kidney is the major regulator of potassium homeostasis. In addition to the ROMK channels, large conductance Ca²⁺-activated K⁺ (BK) channels are expressed in the apical membrane of the aldosterone sensitive distal nephron where they could contribute to renal K⁺ secretion. We studied flow-induced K⁺ secretion in BK channel α-subunit knockout (BK^−/−) mice by acute pharmacologic blockade of vasopressin V₂ receptors, which caused similar diuresis in wild-type and knockout mice. However, wild-type mice, unlike the BK^−/−, had a concomitant increase in urinary K⁺ excretion and a significant correlation between urinary flow rate and K⁺ excretion. Both genotypes excreted similar urinary amounts of K⁺ irrespective of K⁺ diet. This was associated, however, with higher plasma aldosterone and stronger expression of ROMK in the apical membrane of the aldosterone-sensitive portions of the distal nephron in the knockout than in the wild-type under control diet and even more so with the high-K⁺ diet. High-K⁺ intake significantly increased the renal expression of the BK channel in the wild-type mouse. Finally, despite the higher plasma K⁺ and aldosterone levels, BK^−/− mice restrict urinary K⁺ excretion when placed on a low-K⁺ diet to the same extent as the wild-type. These studies suggest a role of the BK channel α-subunit in flow-induced K⁺ secretion and in K⁺ homeostasis. Higher aldosterone and an upregulation of ROMK may compensate for the absence of functional BK channels.