The influence of the guanidine to adenine (G/A) substitution in the promoter region of the apolipoprotein (apo) AI gene (at −75 bp) on serum lipids and apolipoproteins was studied in 287 healthy Chinese of both sexes in Singapore. Women had significantly higher levels of high-density lipoprotein cholesterol (HDLC) and apo AI and lower low-density lipoprotein cholesterol (LDLC). The distribution of genotypes was at Hardy-Weinberg equilibrium. The frequency of the A allele in the Chinese was significantly higher [0.27; 95% confidence interval (CI) 0.24–0.31] than that reported in Caucasians (0.12; 95% CI 0.09–0.14). In men, the A allele was associated with 20% higher apo AI; this association was completely absent in women. Furthermore, in men this association was only observed in those who had never smoked, and was absent in smokers. The G/A substitution explained 9% (P < 0.02) of the sample variance of apo AI in non-smoking men. The modulating influence of smoking could not be examined in women because too few women smoke. Although the impact of this polymorphism is modulated by hormones and smoking, it is of importance in determining levels of apo AI in healthy Chinese individuals. No association of the G/A substitution of the apo AI gene was observed with any other lipid traits. © 1994 Wiley-Liss, Inc.