The serum protein binding of valproic acid (VPA) was examined with samples collected front 88 epileptic patients whose ages ranged from 3 to 78 years.Blood samples were usually collected within one to six hours after a dose in the morning.The free fraction of VPA was obtained with a microultrafiltration devices (Molcut II®) which was developed by Nihon Millipore Ltd., Tokyo, Japan.The free and total VPA levels in serum were determined by fluorescence polarization immunoassay (TDX®).The serum albumin levels were determined by the procedure of ionophoresis.Total VPA levels were positively correlated with free fraction (Y=0.13X+6.39, n=88, r=0.67), and a negative correlation between serum albumin levels and free fraction of VPA (Y=-6.99X+48.49, n=88, r=0.54) was observed in the epileptic patients.We found that the serum albumin levels were decreased with the aging, and the total VPA levels were higher in younger children.The increases of free fraction in the children (8 patients in Lennox Syndrom) and the elderly (11 patients in Hypoalbuminemia) might be results from the protein binding saturation.