1 The effects of a crude fraction of Gymnodinium breve toxin (GBTX) were studied on the rat phrenic nerve diaphragm preparation. 2 Indirectly stimulated muscle contractions were more sensitive to blockade by increasing concentrations of GBTX (0.25 microgram/ml to 10 micrograms/ml) than direct muscle contractions. 3 GBTX increased miniature endplate potential (m.e.p.p.) frequency and depolarized the resting membrane potential of the muscle fibres at the endplate and in non-synaptic regions of muscle fibre. 4 A concentration-dependent biphasic effect on m.e.p.p. amplitude was evident. At lower concentrations m.e.p.p. amplitudes were depressed whereas at high concentrations they were increased. 5 GBTX blocked endplate potentials (e.p.ps) in concentrations (0.5 microgram/ml to 2 micrograms/ml) that did not block m.e.p.ps. 6 Muscle fibre action potentials recorded from cells held at control membrane potential by hyperpolarizing current were not altered by toxin treatment. No repetitive e.p.ps, or muscle action potentials were observed. 7 These data suggest that GBTX may block indirectly stimulated muscle contractions and e.p.ps by depolarizing the nerve terminal in a manner similar to the observed depolarization of the muscle fibre. The depolarization of the nerve terminal may be sufficient to inhibit transmitter release.