Elucidation of the basic mechanisms by which morphine and other opiates produce analgesia could advance the development of more specific analgesic therapies, yet the physiological effects of opiates on central nociceptive substrates have not been established. While it is generally believed that opiates suppress the responses of spinal dorsal horn neurons to noxious stimuli, few studies have actually examined their effects on ascending, nociceptive-specific neurons. In particular, almost no observations have been made on lamina I spinothalamic tract (STT) neurons, which compose about half of this classical pain pathway. The concept that nociceptive- specific and thermoreceptive-specific lamina I STT neurons are an integral component of the central representation of pain and temperature suggests the hypothesis that opiate effects on this pathway, and on its major terminus in the medial thalamus, nucleus submedius (Sm), may be essential actions underlying their effectiveness as analgesics. Thus, this research examines quantitatively the effects of systemic and locally administered morphine on the response characteristics of nociceptive and thermoreceptive lamina I STT cells (and lamina I cells that do not project to the thalamus) and of nociceptive-specific neurons in sm in the anesthetized cat. The identification of selective actions on physiologically distinct subpopulations of lamina I STT neurons will suggest that further analysis of this system could help refine the technique of intrathecal analgesia. The identification of direct opiate effects in Sm will support the possibility that this is a primary site of supraspinal analgesic action, and therefore, of fundamental importance for the eventual development of non-addictive and non-psychoactive central analgesic therapies.