BACKGROUND: The aim of this study was to elucidate the gene dose effect of NAT2 and the effect on the pharmacokinetics of isoniazid (INH) and its metabolites acetylisoniazid (AcINH) in Chinese subjects. METHODS: A total of 24 healthy Chinese subjects, consisting of eight homozygous wild types (wt/wt), eight heterozygous mutants (m/wt) and eight homozygous mutants (m/m) for NAT2, were enrolled in the study. The blood samples (0-14 h) of the subjects were taken after oral administration of a single dose (300 mg) of INH. Concentrations of INH and AcINH in plasma were measured by a reversed-phase HPLC method. RESULTS: The ratio of AcINH and INH (R(A/I)) 3 h post-dose of wt/wt, m/wt and m/m groups were 3.22 ± 1.34, 1.35 ± 0.20 and 0.22 ± 0.06, respectively (p<0.01). The area under concentration-time curve (AUC) values of three groups were 10.35 ± 2.12, 16.34 ± 3.05, 42.24 ± 8.51 mg/h/L for INH and 42.19 ± 8.80, 38.05 ± 5.32, 19.78 ± 3.72 mg/h/L for AcINH, respectively (p<0.01). There was a good linear relationship between pharmacokinetic parameters and the number of active NAT2 genes. CONCLUSIONS: The results suggest that there is a conspicuous gene dose effect in the pharmacokinetics of INH and AcINH. This finding may be valuable in the personalized therapy of tuberculosis with INH.