We examined the effects of the phosphatase inhibitor, okadaic acid, on substance P and calcitonin gene-related peptide release from embryonic rat sensory neurons grown in culture. Exposing isolated sensory neurons to 500 or 1000 nM okadaic acid for 30 min resulted in a 2- to 5-fold increase in the release of either peptide above resting levels and this evoked release was dependent on extracellular calcium. Treating sensory neurons with 250 nM okadaic acid did not alter resting peptide release, but significantly enhanced peptide release evoked by either 50 nM capsaicin, 100 nM bradykinin, or 30 mM KCl. These results suggest that enhancing phosphorylation in sensory neurons is an important component in augmenting transmitter release.