We determined the effect of age on the serum concentration of alpha 1-acid glycoprotein (alpha 1-AGP) in venous blood from 134 subjects who ranged in age from preterm neonates to 18-year-old adolescents. The mean (+/- SD) serum concentration of alpha 1-AGP, determined by radial immunodiffusion, increased significantly with age: the concentration found in neonates was less than that found in infants which, in turn, was less than that found in older children (p less than 0.001). In addition, we determined the effect of alpha 1-AGP on the free fraction of lidocaine in four groups of infants and children who received intravenous lidocaine (1.5 mg/kg). The percentage of free lidocaine correlated inversely and linearly with the serum alpha 1-AGP concentration (r2 = 0.617; p less than 0.001). The percentage of free lidocaine in the five neonates exceeded that in the older age groups. We conclude that the serum concentration of alpha 1-AGP increases while the free fraction of lidocaine decreases from early infancy to adolescence.