An HPLC method for the determination of tetramethylpyrazine in serum and application of this method to tetramethylpyrazine deposition studies in human body were described. Tetramethylpyrazine was extracted from alkalinized serum with dichloromethane using methaqualone as internal standard. A RP mu-Bondapak-C18 (10 microns) column fitted with a variable-wavelength UV spectrophotometer operated at 280 nm was used. The mobile phase was methanol-water (58:42). The detection limit of the method was 0.0174 microgram/ml serum. Assay linearity was shown over the range of 0.0291-5.816 micrograms/ml serum with a regression coefficient of 0.9999. The extraction recovery was 99.84% and no interference was found from endogenous compounds, metabolites of parent drug or other commonly used drugs. For the serum concentration following oral administration of tetramethylpyrazine capsules to healthy volunteers (n = 6), the best fit was found to be with a two compartment open model. After administration of 174.5 mg dose, the pharmacokinetic parameters were as follows: Tp = 0.5102 h, Cmax = 3.114 micrograms/ml, AUC = 5.893 mg/L.h, T1/2 (Ka) = 0.1508 h, T1/2 (alpha) = 0.4855 h, T1/2 (beta) = 2.894 h, C1 = 15.7 L.h-1, Vc = 17.70 L, V = 66.77 L. The results imply that tetramethylpyrazine is absorbed rapidly, distributed widely in the body, and also eliminated at a fairly rapid rate.