The serum concentration of phenobarbital used as an anticonvulsant was monitored in 30 preterm babies. The therapeutic serum concentration was achieved with a loading dose of 20 mg/kg i.v., 10 min after administration. Thirty-six hours after loading, it was possible to maintain therapeutic serum levels with a daily intramuscular dose of 5 mg/kg, avoiding toxicity. A comparison of CSF and serum concentrations indicated that the drug passage to CSF is rapid and depends on a brain lesion. Serum monitoring of phenobarbital is important in preterm neonates under 30 weeks gestation and/or with severe pathological complications.