The effects of several prostaglandins on insulin release were studied during incubation of isolated pancreatic islets from the rat. The glucose-stimulated release of insulin into medium containing 300 mg. per cent glucose and 1.0 mM. theophylline was increased approximately twofold by PGE1, PGE2, and PGF2α. The effect of PGE1was apparent at doses as low as 10−8 M. and progressively increased with concentrations up to 10−5 M. PGA1 did not affect insulin release. Inhibition of insulin release by norepinephrine (10−5 M.) was partially reversed by both PGE1 and PGE2. None of the prostaglandins affected the small basal release of insulin into medium containing 30 mg. per cent glucose. PGE1 (10−5 M.) increased the accumulation of cyclic AMP formed from labeled precursor by pancreatic islets incubated in media containing 10 mM. theophylline and either 30 mg. per cent or 300 mg. per cent glucose. These results indicate that prostaglandins can enhance the release of insulin from beta cellsin response to glucose. This action is antagonistic to the inhibitory effect of norepinephrine on insulin release and may be mediated through effects on adenyl cyclase activity.