Responses of parafasciculus (PF) thalamic neurons to microiontophoretically applied morphine and naloxone were examined in morphine-naive and morphine-dependent rats. The PF neurons exhibited high responsiveness (65%) to microiontophoretically applied morphine. Five different patterns of response to morphine in naive animals were obtained from the PF neurons. In morphine-dependent rats, the total responsiveness to microiontophoretic application of morphine was reduced dramatically (to 30%) and the response patterns to morphine were significantly (P less than .01) altered; this indicates that the PF neurons exhibit tolerance to morphine. Naloxone applied together with morphine only blocked the morphine-induced decreases in firing rates, but not the increases to which naloxone exhibited opiate agonist effects. Microiontophoretic application of naloxone alone, before morphine ejections in morphine-naive rats, induced changes in 51% of the PF neuronal population studied. Most of them (73%) responded with decreased firing rates. In morphine-dependent rats, more units responded to naloxone ejection (64%) as compared with the morphine-naive group. Excitation was the dominant response (73%) to naloxone treatment. The application of naloxone alone in naive and morphine-dependent rats demonstrated that the PF units responded in a characteristic dose-response manner to incremental naloxone administration. The present observations support our previous experiments using systemic applications of morphine and naloxone in freely behaving animals.