The present study shows that systemic capsaicin in adult rats results in a significant loss of axons in the subepidermal nerve plexus of the posterior leg but no loss of axons in the sural nerves of these same animals. These data are interpreted as indicating that the receptive part of the peripheral sensory axon is destroyed but that the cell body and most of the peripheral axon remains intact. Thus we suggest that the receptive part of the peripheral sensory axon is the most vulnerable part of the primary afferent neuron to capsaicin in these animals. These findings may explain the observation that adult rats treated with systemic capsaicin are deficient in their responses to certain painful stimuli but usually do not show obvious signs of primary afferent neuron death. We also suggest that as the dose of capsaicin is increased the whole neuron dies. It remains to be determined if the peripheral damage reported here is related to the striking loss of primary afferent markers in the dorsal horn that is also seen after this treatment.