Thirty-five Sprague-Dawley rats with saphenous neuromas underwent acute microfilament recording in the proximal nerve. The effect of the potassium channel-blocking agents, tetraethylammonium bromide (TEA) and 4-aminopyridine, on spontaneous activity in A fibers terminating in the neuroma was observed. The effects of gallamine were also tested. Of the two channel-blocking agents, TEA reliably increased spontaneous firing in active fibers and initiated spontaneous activity in some fibers with no spontaneous baseline discharge. 4-Aminopyridine had no effect on baseline activity of either spontaneously active or quiescent fibers: however, it inhibited spontaneous activity induced by prior TEA treatment. Gallamine application produced effects similar to TEA in that spontaneous activity was dramatically increased. These results imply that a tonic potassium conductance is present in regenerating fibers in the neuroma and that this conductance moderates the tendency toward hyperexcitability and spontaneous firing. Spontaneous activity in nociceptive afferent fibers may represent the mechanism of chronic pain and paresthesias that often accompany peripheral nerve injury. These results suggest that agents which either increase potassium conductance or selectively inhibit the sodium current in regenerating axons might be effective in the treatment of these chronic pain syndromes.