The effects of a recently synthesized series of aminopyridines 2-methyl-4-AP, 2-chloro-4-AP and 2-(N,N-methyl-benzyl)amino-4-AP (2A-7) on voltage-operated sodium and potassium channels and on the sodium pump activity of non-myelinated fibres of the guinea-pig vagus nerve were studied with the sucrose-gap method. The compound action potential evoked by electrical stimulation and the propagation velocity along the nerve were not affected by 2-methyl-4-AP or 2-chloro-4-AP up to a concentration of 10(-3) M. The post-tetanic potential (PTH) evoked by repetitive stimulation of the nerve and reflecting sodium pumping was also not affected by these agents. The amplitude and duration of the compound action potential were enhanced to some extent by 2-methyl-4-AP at the highest concentration used (3 X 10(-3) M); this action was also observed and was more pronounced with 4-aminopyridine (4-AP). The other aminopyridine 2A-7 (3 X 10(-5) - 3 X 10(-4) M) caused suppression of the compound action potential, a diminished propagation velocity and a reduction of the PTH, an action also observed with lidocaine. These results show that 2-methyl-4-AP and 3-chloro-4-AP did not affect the voltage-operated sodium or potassium channels in non-myelinated fibres of the vagus nerve. Only 2-methyl-4-AP had a small 4-AP-like action at high concentrations. The aminopyridine 2A-7 possesses a local anaesthetic action as reflected by the inhibition of voltage-operated sodium channels.