The effect of stress on prolactin release is still controversial .A number of complex mechanisms may be involved including a possible role of cal¬cium ions and opiate peptides . In this work we tried to study the effect of acute stress on prolactin release and the possible role of calcium Chan¬nels blocker and opiate antagonists on prolactin blood level in normal and stressed rats. 48 rats were included in this study : 24 rats served as con¬trol non stressed rats while the other 24 rats were subjected to acute cold stress. Each group was subdivided into three subgroups : a control group, a group pretreated with a calcium channel blocker (Verapamil) and a group pretreated with opiate antagonist (naloxone). Acute cold stress caused a highly significant increase in prolactin level in blood (P<0.001). Intraperitoneal injection of Verapamil caused a significant increase in pro¬lactin level in non stressed rats (P<0.001) while in stressed rats it caused a significant decrease in prolactin level (P<0.001). In non stressed rats prolactin level showed no significant change after naloxone injection. Which , on the other hand caused a significant decrease in prolactin level in stressed rats (P<0.001) . We conclude that acute stress can increase the prolactin level in blood and that calcium ions and opiate peptides play an important role in the regulation of prolactin release in normal and stressed rats.