The effects of substance P (SP) in rat spinal cord on the humoral immune response to sheep red blood cells (SRBC) were investigated by the hemolytic plaque-forming cell (PFC) technique. Radioimmunoassay was used for assessing SP content. Catecholamines contents were measured by high performance liquid chromatography (HPLC) with electrochemical-detection. The results suggest that SP in the spinal dorsal horn, but not in the lateral horn, could inhibit the thymus-dependent humoral immune response to SRBC, and this inhibitory effect might be related to the influence of dorsal horn SP on thymic activity. Increased SP content in the spinal dorsal horn at the peak of a humoral immune response might suppress the immune response and play a negative feedback role, preventing excessive immune response.