Recently, using intracellular recording techniques, it has been shown that transmitter release from individual varicosities in sympathetic nerves occurs intermittently, and that only a single quantum of transmitter is secreted when the release process of a varicosity is activated by the nerve action potential. Here we discuss results obtained using a novel method of extracellular recording which allows simultaneous measurement of both the nerve action potential and transmitter release from postganglionic sympathetic nerve terminals. We have confirmed that release is intermittent, but the importance of this new approach is that the relationship between the nerve terminal action potential and transmitter release can be studied unambiguously for the first time. Thus, we are able to show unequivocally that: (1) intermittence is caused by a low probability of transmitter release in the invaded varicosity; (2) frequency-dependent facilitation of release is determined by the rate of arrival of the action potential and not by detectable changes in its configuration; (3) the current underlying the excitatory junction potential (EJP) is brief compared to the total duration of the EJP, and (4) clonidine may inhibit transmitter release by modifying the nerve terminal action potential. These results provide important new insights into the fundamental mechanisms involved in the physiological and pharmacological control of transmitter release from sympathetic nerves.