To evaluate the importance of hepatic blood flow in lidocaine kinetics, we compared indocyanine green clearance, an estimate of hepatic plasma flow, to lidocaine clearance in 26 patients, half with and half without congestive heart failure, who received a lidocaine infusion for 24 hours as clinically indicated. The results demonstrated that patients with congestive heart failure had significantly higher steady-state lidocaine levels (6.8 +/- 3.6(S.D.) vs. 2.9 +/- 0.9 microgram per milliliter, P less than 0.005) and reduced lidocaine clearance (3.8 +/- 1.4 vs. 10.9 +/- 3.1 ml per minute per kilogram, P less than 0.005) than patients without heart failure. Potentially subtherapeutic or toxic lidocaine levels were found in 10 patients. The regression line (y = 0.3 + 1.07 x) relating clearance of lidocaine to that of indocyanine green was linear (r = 0.95, P less than 0.001). Since indocyanine green clearance can be determined rapidly and noninvasively, it offers the potential of predicting lidocaine dosage requirements with avoidance of toxicity or suboptimum therapy.