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Department of Physiology, University of Colorado School of Medicine, Denver, CO 80262, U.S.A.

1. The effects of vasoactive intestinal peptide (VIP) on cholinergic transmission were studied at the neuromuscular junction of the frog.

2. Bath application of VIP (10^-8-10^-7 M) produced a dose-dependent increase in quantal content of the end-plate potential (e.p.p.), while having no effect on quantal size or on resting membrane potential of the muscle fibres.

3. The increases in e.p.p. amplitude observed at end-plates blocked with Mg²⁺ or curare were comparable.

4. VIP increased miniature end-plate potential frequency when the nerve terminal was depolarized with K⁺. This effect was abolished by removing Ca²⁺ from the bathing solution.

5. Ionophoretic application of VIP to the end-plate also increased quantal content, while having no effect on quantal size or on the input resistance and resting membrane potential of the fibres.

6. Some possible mechanisms for the action of VIP are discussed, and it is proposed that it may act on some step involved in depolarization—secretion coupling.