Superfusion of rat spinal cord slices with rat interleukin-1β resulted in a significant enhancement of electrically evoked substance P-like immunoreactivity with a maximal effect (> 2-fold increase) at 0.1 ng/ml, whereas higher concentration (10–50 ng/ml) of the cytokine inhibited (≈ 50%) the release of the neuropeptide. Interleukin-1β (0.1 ng/ml) potentiation of substance P-like immunoreactivity release was abrogated by co-perfusion with interleukin-1 receptor antagonist (10–100 ng/ml) or with indomethacin (1 μM). Superfusion of spinal cord with interleukin-1β inhibited electrically evoked calcitonin gene-related peptide-like immunoreactivity release. Modulation of substance P-like immunoreactivity release from the spinal cord by interleukin-1β may represent a mechanism responsible for the hyperalgesic action of the cytokine characteristic of the inflammatory response.