The effects of cyclic GMP (cGMP), carbachol and diltiazem on a potassium-selective, delayed-rectifier current in freshly dissociated rabbit corneal epithelial cells were studied using a modified perforated-patch-clamp technique. The current was stimulated by both 500 microM cGMP (2.3-4.5-fold, mean = 2.9) and 250 nM carbachol, a muscarinic agonist (1.12-7.04-fold, mean = 3.8), and the stimulated current was totally blocked by diltiazem (10 microM). The effects of cGMP appeared to be, at least in part, different from those of carbachol as they required the presence of external calcium. Single-channel data suggest that cGMP and carbachol activate the potassium current by increasing the open probability of the channel via a second-messenger system and that the action of diltiazem is probably through a direct blocking effect on the open channel.