Ionophoretic application of ATP to smooth muscle cells of the rabbit ear artery produced rapid depolarization of the membrane and, in the case of large doses of ATP, spike potentials or slow oscillatory potentials. The ATP response desensitized rapidly, and required over 70 s for recovery. When the intervals between repetitive application of ATP were shorter than 70 s, the amplitudes of the ATP responses successively decreased. Ejection of ATP with increasing intensities of current (10-15% of the first) was required to produce successively increasing amplitudes of ATP responses. Repetitive stimulation of perivascular nerves (at intervals of less than 10 s) evoked increasing amplitude of excitatory junction potentials (e.j.p.s). Quinidine (over 5 X 10(-5) M) inhibited and theophylline (over 5 X 10(-4) M) enhanced the ATP response, with associated depolarization or hyperpolarization of the membrane, respectively. Cocaine (over 10(-6) M) depolarized the membrane and enhanced the ATP response. Phentolamine reduced the amplitude of the ATP response with no change in the membrane potential, only when the concentration was extremely high (over 10(-4) M). These all therefore appear to represent non-specific interactions with the effects of ATP. Bath application of ATP depolarized the membrane dose dependently and, at concentrations over 5 X 10(-7) M, produced spike potentials. The amplitude of electrotonic potentials decreased during the ATP-induced depolarization, thereby suggesting an increase in ionic conductance of the membrane. ADP depolarized the membrane, the effect being weaker than that of ATP. Both AMP and adenosine hyperpolarized the membrane. The results provide evidence that in the rabbit ear artery, the e.j.p. could be mimicked by ATP. ATP can however only account for the fast e.j.p. if it is released in increasing amounts with successive nerve discharges. Reported blocking agents for ATP receptors did not block the response to ATP in this tissue.