A simple MEKC with UV detection at 254 nm for analysis of acyclovir in plasma and in cerebrospinal fluid (CSF) by direct injection without any sample pretreatment is described. The separation of acyclovir from biological matrix was performed at 25 degrees C using a BGE consisting of Tris buffer with SDS as the electrolyte solution. Several parameters affecting the separation of the drug from biological matrix were studied, including the pH and concentrations of the Tris buffer and SIDS. Using dyphylline as an internal standard, the linear ranges of the method for the determination of acyclovir in plasma and in CSF all exceeded the range of 2-50 mu g/mL; the detection limit of the drug in plasma and in CSF (S/N = 3; injection 3.45 kPa, 5 s) was 1.0 mu g/mL. The applicability of the proposed method for determination of acyclovir in plasma and CSF collected at 8 h after intravenous administration of 500 mg acyclovir (Zovirax (R)) in two patients with herpes simplex encephalitis was demonstrated.