The purpose of this study was to assess the influence of acute manic phase on the steady state pharmacokinetics of carbamazepine (CBZ) in bipolar patients. Forty one acutely manic and 76 epileptic patients entered this prospective study. CBZ apparent oral clearance (CL/F) values were calculated in both groups and were compared with each other. CBZ clearance is affected by different factors such as age, body weight, dosage and the use of concurrent medications. However, since these factors were similar between the two groups, our results could not be affected by these confounding factors.Comparison between epileptic and manic patients showed that CL/F values in acutely manic patients were significantly higher than epileptic patients (0.128 ± 0.016 vs. 0.112 ± 0.0147 L/hr/kg, p< 0.0001). As a result, acutely manic patients require more CBZ dosages to achieve serum concentrations comparable with those found in epileptic patients. Increased CBZ clearance in acutely manic patients may be related to increase of catecholamine and sympathetic activity in these patients. This results in increased hepatic blood flow which may affect the hepatic clearance of drug. Besides, due to the abnormalities in membrane transport of acutely manic patients, it may be suggested that cellular uptake of the drug and its volume of distribution may be affected. Since our study is a preliminary investigation in this field, further detailed pharmacokinetic study in acutely manic patients are warranted to confirm results of this study.