In a double-blinded study, 15 American Society of Anesthesiologists class I or II patients, following lateral thoracotomy with general anesthesia, were randomized into two groups for intercostal nerve block with either bupivacaine, 0.5%, and epinephrine, 1:200,000, or plain bupivacaine, 0.5%. Blood concentrations of bupivacaine, epinephrine, and norepinephrine were serially measured. Blood pressure, heart rate, respiratory rate, temperature, and electrocardiogram were monitored. Peak blood bupivacaine concentrations were significantly lower in patients receiving bupivacaine with epinephrine. Peak epinephrine concentrations were significantly greater in patients receiving bupivacaine with epinephrine, but still within a safe range. No significant differences were seen in heart rate, blood pressure, respiratory rate, or temperature between the two groups, and/no dysrhythmias occurred. Peak norepinephrine concentrations were not significantly different between the two groups. The potential risk of toxic bupivacaine blood concentrations associated with intercostal nerve blocks can be reduced by the addition of epinephrine at a concentration of 1:200,000.