Granule cells in the guinea pig dentate gyrus release K opioid neuropeptides, dynorphins, from dendrites as well as from axon terminals. We have found that both L-and N-type calcium channel antagonists inhibited dendritic dynorphin release. In contrast, N-type but not L-type calcium channel antagonists inhibited axonal dynorphin release. Neither L-nor N-type channel antagonists directly altered the effects of K opioid receptor activation. By inhibiting dynorphin release, L-type channel antagonists also facilitated the induction of long-term potentiation of the perforant pathgranule cell synapse. These studies establish that a single cell type can release a transmitter from two different cellular domains and provide new distinction between axonal and dendritic transmitter release mechanisms.