The ability os isoprenaline to enhance transmitter release from sympathetic nerves in rat atria incubated with [3H]noradrenaline was assessed under three conditions of prejunctional alpha-adrenoceptor activation: in the presence of phentolamine, in the presence of noradrenaline, and in the absence of either drug. Isoprenaline-induced enhancement of transmitter release was inversely related to the degree of activation of prejunctional alpha-adrenoceptors. Thus there appears to be an interaction between the prejunctional alpha-adrenoceptor inhibitory mechanism and the prejunctional beta-adrenoceptor facilitatory mechanism. In rabbit ear arteries incubated with [3H]noradrenaline, isoprenaline facilitated transmitter release in the presence but not in the absence of phentolamine. Therefore in some tissues it may be necessary to block prejunctional alpha-adrenoceptors before prejunctional beta-adrenoceptors can be demonstrated.