This study was undertaken to investigate the relationship between dopamine (DA) induced changes in the cytosolic calcium concentration ([Ca2+](i)) and the rate of prolactin secretion using GH(4)ZR(7), a rat pituitary cell line, which express only one subtype of D-2 receptor. GH(4)ZR(7) cells were loaded with Fluo-3, a fluorescent Ca2+ indicator, and then perifused with two different doses of DA (10(-7) mol/L and 5 x 10(-4)mol/L). We monitored changes in [Ca2+](i) and rate of prolactin release simultaneously by attaching a spectrofluorometer to a dynamic perifusion system. DA has stimulatory and inhibitory effect on prolactin secretion in GH(4)ZR(7) cells; 10(-7) mol/L DA slightly increased [Ca2+](i) and stimulated prolactin release, whereas 5 x 10(-4) mol/L DA decreased [Ca2+](i) and inhibited prolactin secretion, When the cells were pretreated with pertussis toxin (PTX), 10(-7) mol/L DA had no significant change in [Ca2+](i) while stimulating prolactin release, and 5 x 10(-4) mol/L DA reduced [Ca2+](i) without having any significant effect on the rate of prolactin secretion. The results of this study demonstrate that changes in [Ca2+](i) do not always correlate with the rate of prolactin release from lactotrophs. The dissociation between [Ca2+](i) and prolactin release is somewhat expected considering the diverse role of [Ca2+](i) and post-[Ca2+](i) events, which can change the rate of prolactin release.