We compared a new coated-particle formulation of valproate (Depakote Sprinkle) capsules with valproic acid (Depakene) syrup for bioavailability, side effects, and patient and parent preference. Twelve children with epilepsy, aged 5 to 16 years, participated in this randomized, two-period, crossover study. They were assigned to a 7-day regimen with one formulation and then crossed over to the other; the drug was given every 12 hours. On day 7, blood samples collected during a 12-hour period were analyzed for the presence of valproate. At the study's end, parents and children were asked structured questions regarding formulation preference and adverse events. The extent of absorption from sprinkle equaled that from syrup (relative bioavailability = 1.02), but absorption was slower (time to maximum concentration = 4.2 vs 0.9 hour; p less than 0.01). Fluctuations in serum concentrations were less with sprinkle (34.8% vs 62.3%; p less than 0.01). Sprinkle was preferred by 9 of the 12 parents because of east of administration, and by nine of the children because of improved palatability. We conclude that sprinkle may be substituted for syrup without changing the daily dose. Furthermore, sprinkle, because of its prolonged absorption, may be given every 12 hours to children receiving monotherapy. Compliance may be enhanced because of the more convenient dosing schedules and the high degree of patient and parent acceptance.