The effects of subcutaneous (s.c.) administration of formalin or carrageenan to the rat hindpaw on the ipsilateral nociceptive flexor reflex was examined in decerebrate, spinalized, unanesthetized rats in order to assess the development of spinal hyperexcitability following peripheral inflammation. Carrageenan induced a weak and brief EMG discharge at the time of injection, followed by a gradual and delayed increase in flexor reflex magnitude, becoming significant 120 min postinjection. In addition, carrageenan induced a decrease in response threshold to peripheral mechanical stimulation as early as 30 min postinjection. Formalin induced an immediate and intense motor discharge which usually decreased after 5-10 min and was followed by a second phase of relatively weak motor discharge lasting for 20-70 min. However, the effect of s.c. formalin on the excitability of the flexor reflex was variable with either facilitation or inhibition. The flexor reflex was significantly depressed after formalin from 90 min post-injection. It is suggested that carrageenan induced prolonged spinal sensitization to nociceptive input, possibly through the induction of peripheral inflammation. In contrast, although formalin generated afferent input and evoked motor discharges, it did not induce significant spinal hyperexcitability. Thus, carrageenan, but not formalin, is useful to study central sensitization following peripheral chemical stimulation and/or inflammation.