PURPOSE: To learn the changes of phenobarbital serum level after intravenous administration of loading dose and to determine the optimal time of maintenance therapy to support therapeutic concentration. METHODS: A total of 24 patients, who were admitted to the pediatric ward for treatment of ongoing and recurrent seizure, were enrolled in this study from November, 1994 to August, 1996. None of them had taken other anticonvulsants before and their age varied from 8 days old to 7 years old. Loading dose of 20mg per kg of phenobarbital was administered intravenously, and sequential plasma samples were obtained at 2, 6, and 12 hours after administration. RESULTS: The mean serum concentration of phenobarbital was 23.65 (11.53-36.81) microgram/ml after 2 hours, 22.78 (10.97-35.29) microgram/ml after 6 hours and 20.79 (9.79-33.01) microgram/ml after 12 hours. We divided the patients into 2 groups by the 12-hour levels, group A : therapeutic level (>20 microgram/ml), and group B : subtherapeutic level. The mean 12-hour level in group A was 25.39 (20.13-33.01) microgram/ ml and 16.24 (9.79-19.48) microgram/ml in group B. The mean 2-hour level in group A was 28.30 microgram/ml and 19.00 microgram/ml in group B (P<0.05). The mean decline rate of serum phenobarbital level was 0.34 microgram/ml/hr in group A and 0.29 microgram/ml/hr in group B. And there was no significant difference between the two groups. CONCLUSION: It is usually effective to begin maintenance therapy 12 hours after loading dose, but in cases where 2-hour serum level of phenobarbital is below 20 microgram/ml, it is better to begin maintenance therapy earlier.