Intramuscular injections of gold sodium thiomalate in the rat produce a significant depletion of the proinflammatory neuropeptide substance P (SP) from the sciatic nerve. The greatest reduction in SP content occurred during the first two months of treatment. The level of SP in the nerve, however, remained low, throughout an eight month administration of gold. These results, coupled with previous findings that gold produces a selective decrease in the number of unmyelinated axons in peripheral nerve, are consistent with the hypothesis that the anti-inflammatory action of gold involves a neurotoxic effect on peptidergic afferents.