Knee joint injection of kaolin and carrageenan produces acute inflammation with localized joint swelling and increased temperature. This inflammation results in behavioral changes, including limping and guarding of the limb, and heat hyperalgesia. Prior spinal cord infusion of bicuculline, a gamma amino butyric acidA (GABAA) receptor antagonist, significantly reduces the severity of joint inflammation and prevents the development of heat hyperalgesia. In contrast, infusion of a GABAB receptor antagonist does not alter the arthritis. Therefore, these data support the existence of a central pathway involving GABAA receptors in the spinal cord that influences the development of peripheral inflammation. We suggest that primary afferent depolarization and accompanying dorsal root reflexes play a significant role in the development of peripheral inflammation.