Repeat determinations of the arrhythmogenic dose of epinephrine (ADE) were made over two 6 h periods on 2 separate days during halothane and isoflurane anesthesia. Each of 6 dogs underwent 4 trials (2 halothane and 2 isoflurane). During each trial, the ADE was determined at baseline, 3 and 6 h. Epinephrine was infused for 3.0 min at increasing dose rates (2.5, 5.0, 10.0 and 20.0 mg/kg/min) until the arrhythmia criterion (4 or more intermittent or continuous premature ventricular contractions) was reached. The inter-infusion interval was 20 min. There were no significant differences in the measured cardiovascular parameters (SBP, DBP, MBP, and HR), arterial blood gases, or acid-base status prior to each determination during a single trial. The cardiovascular responses to epinephrine infusion were not significantly different between inhalants or determinations. The range of the ADE determined over both trials during isoflurane anesthesia was 30.12 +/- 12.21 micrograms/kg to 50.83 +/- 9.17 micrograms/kg. The baseline ADE during Day 1 of halothane anesthesia (6.70 +/- 1.36 micrograms/kg) was significantly greater than ADE determinations at 3 (4.65 +/- 0.88 micrograms/kg) and 6 h (4.61 +/- 0.87 micrograms/kg). The reduction in the ADE over time during day 2 of halothane anesthesia was not statistically significant (P = 0.0669). These results suggest that during halothane anesthesia, the ADE is not repeatable over time, and they may influence our interpretation of the results of investigations that measure alterations in the ADE due to pharmacological manipulations without repeated control ADE determinations.