The effects of [Met5]enkephalin (ME) on the fast excitatory postsynaptic potential (EPSP) in bullfrog sympathetic ganglion cells were studied with intracellular recording in vitro. The variance and failure methods were used to calculate quantal content and quantal size of the fast EPSP in a low Ca2+/high Mg2+ solution. High concentrations of ME (1 and 10 microM) decreased the amplitude and the mean quantal content of the fast EPSP, whereas low concentrations (10 pM to 10 nM) of the peptide increased EPSP amplitude and quantal content. The mean quantal size of the EPSP was not changed by ME. The inhibitory effect of ME at high concentration (10 microM) was reversibly antagonized by the same concentration of naloxone; the facilitatory effect of ME at low concentration (1 nM) was not affected by 10 times higher concentration of naloxone (10 nM), but inhibited by 10 microM naloxone. A low concentration of naloxone (100 pM) itself increased the amplitude and the mean quantal content of the fast EPSP without changing the mean quantal size. The other concentrations of naloxone used in this study (1 pM to 10 microM) caused no significant change in the fast EPSP. ME (100 fM to 10 microM) and naloxone (1 pM to 10 microM) did not change the resting membrane potential or input resistance, the amplitude and duration of action potentials, and the sensitivity to the acetylcholine applied by iontophoresis. These results indicate that ME may act on preganglionic nerve terminals either to facilitate or to depress transmitter release; the inhibitory action is naloxone sensitive, whereas the facilitatory action is less sensitive to naloxone.