The post-tetanic hyperpolarizations (PTHPs) were recorded from the isolated bullfrog sciatic nerves using a modified vaseline gap method. Repetitive stimulation of tetrodotoxin-resistant (TTX-R) C-fibers produced frequency- and activity-dependent PTHPs. The ouabain solutions (0.1 mM), the solutions (0.1 mM ouabain + 2 mM tetraethylammonium (TEA)) and 5 mM TEA solutions reduced the PTHP amplitude to 56.2 +/- 10.7% (mean +/- SD, n = 9), to 37.0 +/- 12.3% (n = 8), to 76.0 +/- 10.9% (n = 5) of the control value, respectively. Each pair of the three solutions revealed a significant difference in their effects on the PTHP (P < 0.01). Furthermore, the Li-Ringer solutions and the solutions (Li-Ringer + 2 mM TEA) reduced the PTHP amplitude as well, thus resembling ouabain effects. These results strongly suggest that the repetitive stimulation of TTX-R C-fibers activates the membrane Na+-K+ pump resulting in a major part of the PTHP and induces TEA-sensitive K+ conductance composing a minor part of the PTHP, which might modulate repetitive firing of TTX-R C-fibers.