Lidocaine plasma levels and indocyanine green clearance were measured in five normal volunteers and eight patients admitted to the coronary care unit. All individuals received lidocaine as a 1 mg/kg bolus and a 35 microgram/kg/min constant infusion for 180 minutes. Eight of the 13 (62 per cent) individuals studied (all normal volunteers and three patients) developed early, potentially subtherapeutic plasma lidocaine levels (less than or equal to 2.4 microgram/ml) within 15 minutes after starting therapy. Those individuals with subtherapeutic levels had either minimal (American Heart Association Class) or no clinical evidence of congestive heart failure. The use of indocyanine green (ICG) clearance as an estimate of hepatic plasma flow showed that individuals with early, subtherapeutic lidocaine levels had higher ICG clearance (9.33 +/- 0.32 ml/min . kg versus 2.90 +/- 1.74 ml/min . kg) and shorter ICG t 1/2 (2.02 +/- 0.99 minutes versus 3.6 +/- 0.69 minutes) and larger volume of distribution (36.1 +/- 16.3 ml/kg versus 19.5 +/- 12.8 ml/kg) than patients without subtherapeutic levels. This study suggests that early lidocaine kinetics may be significantly altered by clinical conditions that alter hepatic blood flow. The reappearance of arrhythmias shortly after initiating lidocaine therapy in patients without heart failure may be due to rapid hepatic clearance and subtherapeutic blood levels rather than lidocaine-resistant arrhythmias.