The purpose of this study was to evaluate the effect of congenital heart disease (CHD) on the serum concentrations of alpha 1-acid glycoprotein (alpha 1-AGP) and the serum binding of lidocaine. Thirteen children with acyanotic CHD and 12 children with cyanotic CHD were studied and compared with 28 children without heart disease (control). The mean (+/- SD) serum concentration of alpha 1-AGP, as determined by radial immunodiffusion, did not differ significantly among the three groups. Five minutes after administration of 1.5 mg.kg-1 intravenous lidocaine, the free fraction of lidocaine correlated inversely and linearly with the serum concentration of alpha 1-AGP in children with acyanotic CHD (r2 = 0.74; P less than 0.001) cyanotic CHD (r2 = 0.57; P less than 0.005), and control (r2 = 0.63; P less than 0.001). The slopes and intercepts of the linear regressions did not differ significantly among the three groups. We conclude that the serum concentration of alpha 1-AGP in children with CHD does not differ quantitatively or qualitatively from that in children without CHD.