To determine hepatic drug metabolism in patients with cystic fibrosis, as measured by monoethylglycinexylidide formation after lidocaine injection and indocyanine green (ICG) clearance. The following study is a case-control study, which included 19 patients with cystic fibrosis and 13 control subjects. Serum monoethylglycinexylidide concentration was measured after intravenous injection of 1 mg/kg (maximum, 50 mg) lidocaine. Indocyanine green (0.5 mg/kg) was injected concomitantly, and absorbance (805 nm) of serum was measured over time to determine its volume of distribution, serum half-life, and hepatic blood flow. Monoethylglycinexylidide formation was decreased in patients with cystic fibrosis compared with controls (39.4+/-16.9 microg/L versus 70.3+/-45.7 microg/L, mean +/- SD, respectively, P < 0.02). Indocyanine green half-life (4.6+/-2.7 min versus 3.0+/-1.0 min), volume of distribution (8.6+/-5.5 L versus 8.3+/-3.4 L), and hepatic blood flow (10.9+/-5.9 ml x kg(-1) x min(-1) versus 7.4+/-2.0 ml x kg(-1) x min(-1)) were similar in both groups. Monoethylglycinexylidide formation after lidocaine injection is impaired in patients with cystic fibrosis. This impairment may have clinical implications when using hepatically metabolized medications in patients with cystic fibrosis.