The oral dose recommendation for FK506 (Fujisawa Pharmaceutical, Deerfield, IL) after liver transplantation has, to date, made no distinction between adult and pediatric patients. Sixteen pediatric and 33 adult liver transplant patients treated long term with oral FK506 were studied. Initial FK506 doses were 0.3 mg/kg/day p.o. or 0.15 mg/kg/day i.v. Thereafter, doses were adjusted to achieve therapeutic FK506 serum levels (0.5-3.0 ng/ml, ELISA liquid/liquid separation) and to maintain an acceptable serum creatinine. FK506 (in mg/kg/day), FK506 levels, and liver function were assessed at monthly intervals on outpatient visits. The mean age of 16 pediatric patients was 5.3 +/- 3.5 years and of 33 adult patients was 49 +/- 12 years. Mean days of FK506 therapy were 284 +/- 136 for pediatric patients and 239 +/- 112 for adult patients. For each time period, pediatric patients required a significantly higher dose of FK506 compared to adult patients (P < 0.001). The overall mean pediatric dose for the first year was 0.46 +/- 0.4 mg/kg/day compared to the mean adult dose of 0.13 +/- 0.01 mg/kg/day. The ratio of pediatric to adult oral FK506 dose requirements ranged from 2.7 to 4.4 over the 1 year of followup. FK506 levels monitored at the same time points showed no significant differences at any month between pediatric and adult patients. We conclude that the oral dose per kilogram per day of FK506 required to maintain similar FK506 levels is significantly greater in pediatric patients compared to adult recipients during the first year of follow-up. Pediatric recipients require substantially more, and adult recipients substantially less, than the recommended oral FK506 dose to achieve a therapeutic effect.