Some primary nociceptor neurons produce and release substance P (SP), a peptide neurotransmitter with well-described effects on second-order sensory neurons. However, the effects of SP on primary sensory neurons are less clear. We tested the hypothesis that SP acts on an autoreceptor by examining the pharmacological profile of rat DRG neurons sensitive to SP. Whole-cell patch clamp was used to measure the response of 89 cells to brief applications of pH 7 (27 positive cells), pH 6 (37 positive cells), capsaicin (22 positive cells), and ATP (15 P2X3 type positive cells). Sensitivity to SP was determined by an increase in cell excitability measured as the number of action potentials at the threshold and the slope of the stimulus-response curve (16 positive cells). There was also a decrease in excitability in 8 cells. Among the cells responding to SP by increasing excitability, the frequencies of sensitivity to pH 7 (67%) and pH 6 (88%) were higher than in non-responding cells (24% and 32 % respectively, p<0.01). The frequencies of sensitivity to capsaicin had a tendency to be higher in the SP responding cells (38% versus 22%, p=0.33). P2X3 type ATP currents were present in 15 of 73 (21%) SP non-responding cells, while none of the 16 SP positive cells presented this current (p=0.1). We conclude that the majority of SP sensitive neurons exhibit a pharmacological profile typical of nociceptors, although P2X3 currents were not present in these cells.