To understand better the hemodynamic effects of fentanyl anesthesia on the developing newborn, the authors studied the changes in cardiac output and its four determinants (preload, afterload, heart rate, and contractility) and plasma fentanyl kinetics in newborn piglets following the administration of high-dose fentanyl with or without atropine premedication. Twenty-five healthy farm piglets were divided into four groups. Hemodynamic studies were conducted on five who received 50 micrograms/kg intravenous fentanyl, five controls who received only 0.01-0.03 mg/kg intravenous atropine, and nine who received both agents. Fentanyl pharmacokinetics were determined by radioimmunoassay in six additional piglets. Mean plasma fentanyl concentrations were 25.4, 12.7, and 7.9 ng/ml at 5, 15, and 30 min postbolus, respectively, with an elimination phase half-life of 35.8 min. In piglets given fentanyl alone, the maximum significant (P less than 0.05) hemodynamic changes from baseline occurred at 5 min: mean aortic pressure (MAP) +42%, cardiac output -42%, heart rate -36%, left ventricular end-diastolic pressure +81%, and total peripheral resistance index +93%. The latter four hemodynamic variables were highly correlated with the logarithm of the plasma fentanyl concentration (R2 greater than 0.96, P less than or equal to 0.05). In control animals given atropine alone, only MAP changed significantly (+12-14%) during the study. Contractile indices (echocardiographic shortening fraction and left ventricular peak dP/dT) did not change significantly in any group. Piglets given fentanyl-atropine had no significant hemodynamic change during the study other than a 7-15% increase in MAP.