The design and implementation of a computer-assisted continuous infusion (CACI) system to rapidly attain and maintain a constant plasma fentanyl concentration (PFC), as well as a CACI system that allowed the anesthesiologist to change the plasma level of fentanyl during cardiac anesthesia, were developed. In 30 patients (three groups of 10 patients each) these two automated methods of fentanyl infusion were compared with a manual fentanyl administration method. There was excellent agreement in the measured/predicted PFC ratios with the CACI stable fentanyl level system (ratio = 0.99, n = 91) and in the CACI variable fentanyl level system (ratio = 1.08, n = 79). The stable fentanyl level group of patients received significantly more (P< 0.05) fentanyl than did the other groups. The CACI variable fentanyl level group of patients had greater hemodynamic stability, required significantly (P< 0.05) fewer adjuvant drug interventions and experienced significantly (P< 0.05) fewer hypotensive and hypertensive episodes than the manual, bolus fentanyl (control) group. These data show that a computer-assisted automated infusion of fentanyl is safe and as good as manual methods. CACI has greater potential as a new method of intravenous anesthesia administration.