The involvement of NMDA receptors in rats with peripheral inflammation and hyperalgesia was evaluated by administration of the non-competitive NMDA receptor antagonist, MK-801. Inflammation and hyperalgesia was induced by intradermal injection of complete Freund's adjuvant (CFA) or carrageenan into the left hind paw. The latency of paw withdrawal from a thermal stimulus was used as a measure of hyperalgesia in awake rats. MK-801 (1.6 mg/kg, i.p., or 31.5 micrograms, intrathecal) significantly attenuated thermal hyperalgesia and reduced its duration in comparison to saline-injected rats (P less than 0.05). The receptive field size of nociceptive-specific and wide-dynamic-range neurons in the superficial and deep spinal dorsal horn recorded 24 h after injection of CFA was significantly reduced to 73 +/- 6% (P less than 0.05, n = 8) and 74 +/- 4% (P less than 0.05, n = 8) of control values, respectively, by a cumulative dose of 3 mg/kg of MK-801 (i.v.). MK-801 (2 mg/kg) prevented the expansion of the receptive fields of dorsal horn neurons recorded 5 +/- 0.4 h (n = 5) after intradermal injection of CFA as compared to saline-injected rats (P less than 0.05). MK-801 had no significant effect on receptive field size of dorsal horn neurons in rats without CFA-induced inflammation but blocked a transient expansion of the receptive fields induced by 1 Hz, C-fiber intensity electrical stimulation of the sciatic nerve. The background activity and noxious heat-evoked response of dorsal horn neurons in rats with CFA-induced inflammation were primarily inhibited and noxious pinch-evoked activity was both facilitated and inhibited by the administration of MK-801. These results support the hypothesis that NMDA receptors are involved in the dorsal horn neuronal plasticity and behavioral hyperalgesia that follows peripheral tissue inflammation.