Serotonin modulates neurotransmission at synapses between various spinal neurons and, thus, may either facilitate or depress the information processed in the circuits and ultimately modulate the final motor output. A possible neuromodulatory role of 5-hydroxytryptamine type 1A (5-HT1A) receptors on the excitability of lumbar spinal Renshaw cells was explored in anesthetized rats spinalized at T4 level. Intravenous administration of the specific 5-HT1A agonist (2R)-(+)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT) (0.1 mg/kg) decreased the Renshaw cell burst response by 20–45%. This effect was completely antagonized by the specific 5-HT1A antagonist (S) -N-tert-butyl-3- (4-(2 -methoxyphenyl) - piperazin-1-yl) -2 -phenylpropanamide dihydrochloride [(S)-WAY 100135] (0.1 mg/kg, intravenous), although this drug per se had no effect on the Renshaw cell burst response. These results suggest that 8-OH-DPAT-induced decrease in Renshaw cell burst firing was mediated by 5-HT1A receptors located either presynaptically or postsynaptically.