The effect of ethanol on neuromuscular transmission in the isolated phrenic nerve-diaphragm preparation of the rat was studied by analysing its effect on directly- and indirectly-elicited twitch tension, tetanic and post-tetanic twitch tensions, and on the phenomenon of post-tetanic twitch potentiation (PTP). The results show that ethanol (1.0 X 10(-4)-1.0 M) depresses neuromuscular transmission, by reducing the amplitudes of both directly and indirectly elicited twitch and tetanic contractions. Ethanol produces a greater reduction in the amplitude of indirectly- than directly-elicited twitch tension and the mean concentration of ethanol which produced a 50% reduction was 38 mM. High concentrations of ethanol (greater than 10(-3) M) completely blocked the indirectly-elicited twitch tension in 4 min exposure. Ethanol also reduced the tetanic tension and increased the PTP value. There was no tetanic fade in the presence of ethanol, but the peak tetanic tension was reduced by 20-50%. It is suggested that ethanol inhibits neuromuscular transmission in the rat phrenic nerve-diaphragm preparation, possibly via a mixture of pre- and postjunctional mechanisms and produces a greater reduction in the twitch than tetanic tension.