Guinea pig pancreatic segments were superfused during 10 min with physiological saline solutions containing 10(-6) M acetylcholine (ACh) or histamine (10(-3)-10(-6) M) and the potassium concentration in the effluent [K+]o) was measured by flame photometry. Histamine evoked a transient increase in [K/]o. The removal of calcium from the superfusing solution and addition of 10(-4) M EGTA caused a significant reduction in the histamine-evoked potassium outflow. Replacement of chloride (Cl-) in the physiological salt solution by nitrate (NO3-) caused a significant reduction in the histamine-evoked potassium release. However, when Cl- was replaced by bromide (Br-) the response to histamine was unaffected. Pre-treatment of pancreatic segments with furosemide (10(-4 M) or ouabain (10(-3) M) caused a marked reduction in the histamine-induced potassium release. The results suggest that ionic requirements in histamine-evoked potassium release are the same as those in acetylcholine-evoked potassium efflux.