Dissociated bullfrog dorsal root ganglion cells were voltage clamped in the whole-cell configuration. In small C-cells having 20 microns as averaged diameter, substance-P (0.1-1 microM) inhibited an M-type potassium current while ATP (1-10 microM) activated a sodium-potassium current. In large A-cells (approximately 65 microns in diameter) in which ATP has been shown to inhibit M-current, substance P (0.1-1 microM) also inhibited this potassium current without activating the sodium-potassium current. Results provided evidence for the distinction between A- and C-cells in terms of their chemosensitivity.