We used the patch-clamp technique to study the effects of angiotensin II (ANG II) on basolateral K channels in cortical collecting ducts (CCDs). Application of ANG II (100 pM–100 nM) increased the activity of basolateral 18-pS K channels. This effect of ANG II was completely abolished by losartan, which is an antagonist of type 1 angiotensin (AT₁) receptors. In contrast, inhibition of type 2 angiotensin (AT₂) receptors did not block the stimulatory effect of ANG II. Also, application of ANG II significantly increased intracellular Ca²⁺ concentrations, which were measured with fura 2 dye. To explore the role of Ca²⁺-dependent pathways in the regulation of basolateral K channels, the effects of ANG II on channel activity were examined in the presence of arachidonyltrifluoromethyl ketone to inhibit phospholipase A₂ (PLA₂), GF-109203X [a protein kinase C (PKC) inhibitor], andN ^G-nitro-l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthase. Inhibition of either PLA₂ or PKC did not block the effect of ANG II on basolateral K-channel activity. However, the stimulatory effect of ANG II was absent in the CCDs treated with l-NAME. Moreover, addition of the membrane-permeant 8-bromo-guanosine 3′,5′-cyclic monophosphate (8-bromo-cGMP) not only increased channel activity but also abolished the stimulatory effect of ANG II on channel activity. We conclude that ANG II increases basolateral K-channel activity via the stimulation of AT₁ receptors, and the stimulatory effect of ANG II is mediated by a nitric oxide-dependent cGMP pathway.