We measured the apparent half-life (t50%) of phenytoin (PHT) 30 times in 16 infants (aged 2 to 36 days) who had seizures. During the first week of life, the t50%s ranged from 6 to 140 hours. After the first week, the concentration dependence of PHT elimination was demonstrated; the t50% was related to the initial concentration (Ci). The t50% also decreased with postnatal age. Controlling for a Ci of 18 mg per liter, the average t50% decreased threefold between the first (57.3 +/- 48.2 hours) and fourth weeks (19.7 +/- 1.31). In newborns, both age-related changes and the concentration dependence of PHT elimination can cause PHT levels to decrease when constant doses are given.