We studied the effects of the high-efficacy 5-hydroxytryptamine1A (5-HT1A) receptor agonist, F 13640 on both formalin-induced spinal cord c-Fos protein expression and pain behaviours in the rat. Replicating earlier data, F 13640 (0.63 mg/kg, i.p.; t(-15 min)) completely inhibited the elevation and licking of the formalin-injected paw. In the same animals, and in spite of the agent as in earlier data increasing the number of c-Fos labelled nuclei when it was administered alone, F 13640 markedly reduced the number of formalin-induced c-Fos labelled nuclei. This was found in both the superficial (I-II) and deep (V-VI) dorsal horn laminae (2 h post-injection: 72+/-2% and 92+/-1% of reduction, respectively; P<0.001 in either case), spinal areas that contain neurons responsive to nociceptive stimulation. Co-operation occurred so that after the co-administration of F 13640 and formalin, c-Fos expression was inferior to that induced when either stimulation was administered alone. The data provide initial evidence for the agent's inhibitory effects on noxiously evoked c-Fos expression. The results indicate that co-operation between 5-HT1A receptor activation and nociceptive stimulation powerfully inhibits responses to severe, tonic nociception.