The effects of luteinizing hormone releasing hormone (LHRH) on cholinergic transmission were studied at the neuromuscular junction of the frog. Brief application of LHRH produced a prolonged increase in the amplitude of end-plate potentials (e.p.p.s), which lasted 20 to 30 min after removal of LHRH. LHRH (0.4-1 microM) increased in the quantal content of the e.p.p. dose-dependently, while having no effect on the quantal size. LHRH (0.4-1 microM) did not affect the frequency and the amplitude of miniature end-plate potential (m.e.p.p.). At a high concentration (8 microM), however, LHRH consistently produced an increase in the frequency and a decrease in the amplitude of m.e.p.p. The acetylcholine-induced end-plate current (ACh current) produced by iontophoretic application of ACh was reversibly and dose-dependently reduced by LHRH (4.6-46 microM). An analysis with a dose-response curve of the ACh current revealed that LHRH decreased the sensitivity of the nicotinic receptor in a noncompetitive manner. These results suggest that LHRH at low concentrations facilitates neuromuscular transmission by increasing ACh-release from the presynaptic nerve terminals, while at higher concentrations it depresses transmission post-synaptically. Possible mechanisms of these LHRH actions are discussed.