We have monitored cytosolic [Ca2+] with fura-2 and exocytosis by measuring the membrane capacitance, and we have studied the influence of cytosolic [Cal2+] on secretion in single endocrine cells. As in neurons, cytosolic Ca2+ is sufficient to trigger exocytosis. The rate of secretion grows with the fourth or fifth power of cytosolic [Ca2+], and paired stimuli reveal facilitation. Cal2+ influx through voltage-sensitive Cal2+ channels can stimulate secretion 1000-fold over the basal levels measured biochemically. Unlike neurons, however, melanotrophs continue to secrete for seconds after a depolarizing pulse, while they extrude or sequester the Cat2+ that has entered through Cat+ channels. Following episodes of secretion, pituitary cells can retrieve membrane with half-times around 30 s at 32°C, even in the absence of cytosolic K+.