The ability of acute, short-term, inspiratory flow-resistive loading to generate endogenous opioids was studied in 6 unanesthetized goats. Endogenous opioid generation was assessed by measurement of immunoreactive beta-endorphin levels in the cisternal cerebrospinal fluid (CSF) after high (80 cm H2O/L/s) and moderate (50 cm H2O/L/s) resistive loading. The results show that CSF levels of beta-endorphin were significantly increased by both the high and moderate resistive loads (40 +/- 4 SEM pg/ml and 33.7 +/- 3.4 pg/ml, respectively) when compared with the same animals during unloaded control conditions (19.5 +/- 3.8 pg/ml). Both levels of loading also caused a significant progressive decline in tidal volume (to 82 +/- 8 and 89 +/- 8% of baseline tidal volume with the high and moderate loads, respectively). Naloxone administration (0.1 mg/kg) resulted in a transient but significant increase in tidal volume from the sixth through the twentieth minute (to 37 +/- 5 and 34 +/- 5% peak tidal volume increase with high and moderate loads, respectively). In addition, there was a significant correlation between the percent decline in tidal volume and mean inspiratory flow rate after loading and the level of beta-endorphin in the cisternal CSF. We conclude that relatively short-term, high-level, inspiratory flow-resistive loading results in elaboration of endogenous opioids within the central nervous system and that these opioids play a role in the progressive decline in tidal volume and mean inspiratory flow rate exhibited during these conditions.