The effects of several anesthetic drugs and artificial respiration on the release of pituitary beta-endorphin-like immunoreactivity (beta-END-LI) were examined in rats. Plasma beta-END-LI responses to halothane and pentobarbital were similar in magnitude and duration, being maximal (2- to 3-fold) by 10 min and returning to control values by 30 min after induction. Urethane anesthesia was associated with an 8-fold increase in plasma beta-END-LI throughout the 30-min treatment period. In comparison to anesthesia alone, anesthesia plus intubation with artificial respiration (standard parameters) was associated with considerably greater elevations in plasma beta-END-LI (up to 30-fold). Further, intubation and artificial respiration appear to have contributed separately, and in an additive fashion, to the overall beta-END-LI responses observed. As compared to halothane anesthesia alone, intubation evoked a 4-fold increase in circulating beta-END-LI, whereas intubation plus ventilation was associated with a 12-fold increase. Treatment with morphine (1 or 5 mg/kg), but not pancuronium (0.3 mg/kg), attenuated the plasma beta-END-LI response to mechanical ventilation, suggesting that a subconscious phenomenon, perhaps related to pain, was partially responsible for the profound release of pituitary beta-END-LI associated with artificial respiration. Chromatographic analysis of the molecular forms of beta-END-LI released into plasma revealed that both beta-END- and beta-lipotropin (beta-LPH)-sized peptides were secreted under the present experimental conditions. Since the analgesic form of beta-END (beta- END1 -31) is cosecreted with beta-LPH from the pars distalis, increases in the fraction of plasma beta-END-LI corresponding to beta-END in size were probably due to the release of opiate active beta- END1 -31.