Naloxone treatment of endotoxin shock has been shown to alter many cardiovascular parameters. However, since opioids can affect ventilatory function we thought it important to assess the effects of naloxone on some respiratory variables during endotoxin shock. Male Sprague-Dawley rats (300-400 g) were surgically prepared with carotid artery and jugular vein cannulas 24 hours before experiments were begun. Conscious, unrestrained rats were challenged with 10 mg/kg E. coli endotoxin or saline. Measurements of blood gases, pH, respiratory rate, serum lactate, and medullary/pontine blood flow (radio labelled microsphere method) were made 0, 10, 30, and 60 minutes postchallenge. Rats were treated with either 2 mg/kg naloxone or saline at 25 minutes postchallenge. Arterial PO2 rose and PCO2 fell in a stepwise fashion in saline-treated endotoxic rats. These changes were unrelated to medullary/pontine perfusion or to arterial pH (up to 30 minutes postchallenge). In naloxone-treated endotoxic rats the increased ventilatory drive at 60 minutes was attenuated, apparently as a result of prevention of acidosis at this time. These data further support uncoupling of ventilatory drive and arterial pH reported earlier and also indicate that naloxone's ability to prevent acidosis in these animals is not mediated through respiratory compensation.