The distribution of five restriction fragment length polymorphisms (RFLPs) of the APOA1-C3 gene cluster and their influence on serum lipids and apolipoprotein levels was investigated in 151 healthy Chinese of both sexes. The frequencies of the rare alleles at ApaI, BanI, Xmnl (Al) and SstI (C3) sites were significantly different in the Chinese when compared to Caucasians as follows: ApaI: 0.25 vs. 0.42 (p& < 0.02); BanI: 0.33 vs. 0.16 (p& < 0.01); XmnI: X2, 0.30 vs. 0.14, and X3, 0.08 vs. 0.05 (p = 0.001); Sstl (C3): 0.23 vs. 0.12 (p = 0.01). The frequency of P2 (Pstl) at 0.04 was similar to that in Caucasians (0.07). The distribution of the genotypes of all the RFLPs was in Hardy-Weinberg equilibrium in this population. A significant association of the Sstl polymorphism of the C3 region with the serum high-density lipoprotein (HDL)-cholesterol level was observed in both men and women, the rarer allele (S2) being associated with higher levels (p < 0.05). 5.8% of the sample variance of the HDL-cholesterol level in this sample could be explained by the Sstl polymorphism of the C3 region (F = 6.07, p = 0.003). The association of the Sstl locus with serum HDL-cholesterol was stronger in males than in females (R2 = 13.8 and 6.7%, respectively). There was a similar trend of association of the serum apolipoprotein A-I level with the Sstl polymorphism, though it did not reach statistical significance. There was no association between the levels of any of the lipid and apolipoproteins studied with RFLPs of the APOA1 gene.