Cytochrome P450s are a superfamily of enzymes that participate in the metabolism of various xenobiotics and endogenous compounds. An increasing number of studies demonstrate that human P450 enzymes are highly polymorphic. In 2001, Chevalier 'et al.' reported four human 1A2 allelic variants (D348N, 1386F, C406Y and R431W). The present study was to investigate the effects of these mutations on the enzyme expression and activity. Four variants displayed different expression of holoenzymes in 'Escherichia coli': compared with wild type, expression was slightly lower in C406Y, less than half in D348N and I386F, and undetectable in variant R431W. Activities for the activation of procarcinogens MeIQ (2-amino-2,4-dimethyl-imidazo[4,5-' f']quinoline) and IQ (2-amino-3-methylimidazo[4,5-'f']quinoline) were roughly agreed with their expression levels, with complete loss of catalytic ability in variant R431W. The values of 'kcat/K' M of 'N'-hydroxylation of five aromatic amines and ' O'-deethylation of phenacetin varied from 0.1- to 3.0-fold of the wild type. Results from this study show that the residue R431, located in the "meander" region, is critical for human P450 1A2.