This study was designed to investigate the effects of etomidate and its solubilizing agent (propylene glycol) upon enflurane metabolism and adrenal steroidogenesis in Fischer 344 rats. A central venous catheter was placed using pentobarbital anesthesia, and rats were randomized to one of four groups for treatment several days later. Group 1 animals received normal saline, 3 ml/kg, given via the central venous catheter. The other three groups were administered equivalent volumes of either: crystalline etomidate (group 2), 0.4 mg/ml, in saline and 1.1% ethanol; propylene glycol (group 3), 7%, in saline; or etomidate (group 4), 0.4 mg/ml in saline with 7% propylene glycol. In the first part of this study, after an intravenous bolus of one of these four solutions, animals were immediately placed in a 200-liter chamber and received 1 h of 2% enflurane. Serum and urine were assayed for inorganic fluoride (F-) before and after anesthesia. Two hours after enflurane anesthesia, groups 1 and 2 had the highest mean peak serum F- concentrations (13.2 and 13.5 uM, respectively). Groups 3 and 4 had significantly lower mean peak serum F- concentrations (4.7 and 4.5 uM, respectively). In the second part of this study, additional animals were randomized into four groups and received the same intravenous medications as above. Thirty minutes later, they received an intravenous bolus of ACTH. Blood samples were drawn and serum aldosterone levels were measured. Animals in groups 1 and 3 had significantly greater increases in peak serum aldosterone levels 30 minutes after ACTH (peak levels: 0.80 and 0.77 ng/ml, respectively) than animals in groups 2 and 4 (peak levels: 0.60 and 0.58 ng/ml, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)