1. Pentobarbitone or phenobarbitone, in increasing concentrations up to 0-5 mM, progressively reduced the amplitude of miniature end-plate potentials (min.e.p.p.s). Pentobarbitone was the more potent of the two barbiturates in this regard. 2. Both barbiturates produced a monotonic increase in mean quantum content of the end-plate potential (e.p.p.) with increasing concentrations up to 0-5 mM. Pentobarbitone and phenobarbitone were equally potent in their action on evoked transmitter release. 3. The effect, if any, of increasing concentrations of barbiturates on the e.p.p. amplitude was depression. Therefore, over the range of concentrations examined the enhancement of transmitter release was quantitatively less than the reduction in responsiveness of the post-synaptic membrane. 4. Because of the greater ratio of post-synaptic to presynaptic actions, pentobarbitone was more potent than phenobarbitone in reducing synaptic efficacy (e.p.p. amplitude). 5. It is concluded that the presynaptic actions of pentobarbitone and phenobarbitone contribute significantly to barbiturate-induced changes in synaptic efficacy at low levels of transmitter release in the frog neuromuscular junction.