The possible involvement of sodium action potentials in sympathomimetic effects of nicotine was investigated using isolated guinea-pig aortas. Goniopora toxin (GPT), a polypeptide isolated from coral, was used to increase the sodium influx through the fast sodium channel of the postganglionic sympathetic nerves; tetrodotoxin (TTX) was used to block this flux. Nicotine (10-300 microM) produced sympathetic nerve-mediated contractions in a concentration-dependent manner. GPT (30 nM) enhanced the responses to nicotine over the entire range of concentrations tested, yet there was no effect on resting tension. Such an effect of GPT was concentration-dependent and was apparent in concentrations over 10 nM. GPT had no effect on the responses to exogenously applied norepinephrine. TTX (100 nM) abolished this potentiating effect of GPT, but did not inhibit the usual nicotine-induced responses. The 3H-efflux induced by nicotine (100 microM) in the preparations preincubated with [3H]norepinephrine was not significantly inhibited by TTX (100 nM). GPT (30 nM) markedly augmented nicotine-induced 3H-efflux and TTX prevented this effect of GPT. These results appear to indicate that the augmentation of the nicotine-induced response by GPT in isolated guinea-pig aortas is due to a prolongation of the duration of the presynaptic action potential. The effects of nicotine on adrenergic nerve terminals may involve two mechanisms, i.e.: 1) one mediated by sodium action potentials and 2) one independent of these action potentials.