Background: It is generally accepted that apolipoprotein (apo) A-1 is the dominant structural apolipoprotein of HDL particles and different HDL subclasses have distinct but interrelated metabolic functions. HDL is known to directly affect the atherogenic process hence changes in HDL subclasses distribution may be related to the incidence and prevalence of atherosclerosis. Methods: The ApoA-I contents (mg/l) of plasma HDL subclasses were determined by 2-dimensional gel electrophoresis coupled with immunodetection and apoA-I genotypes were assayed by PCR-RFLP in 307 Chinese subjects (169 mates, 138 females). Results. The G/G and C/C genotypes were the most frequent at - 78 bp and +83 bp of apoA-I gene, respectively. There were no significant differences in the frequencies of rare A allele at - 78 bp and rare T allele at +83 bp between males and females. Compared with the G/G carriers, G/A and A/A carriers had significantly higher plasma concentrations of TG, apoC-II, apoC-III, apoA-I contents of pre beta(1)-HDL, HDL3a and TG/HDL-C ratio. And in addition, A/A carriers had significantly lower apoA-I contents of HDL2a and HDL2b. Females had increased plasma concentrations of apoA-I, HDL-C, apoA-I contents of HDL2a. and HDL2b while decreased apoA-I contents of pre beta(1)-HDL, HDL3b and TG/HDL-C ratio as compared to males carrying the same genotype. No significant differences were demonstrated on the concentrations of plasma lipids, lipoproteins, apolipoproteins and apoA-I contents of plasma HDL subclasses between the C/C and C/T subjects. Conclusion: The G/A polymorphism at - 78 bp of apoA-I gene was associated with changes of HDL subclasses distribution. There was a general shift towards smaller-sized HDL, which, in turn, indicated that reverse cholesterol transport (RCT) might be weakened and HDL maturation might be abnormal in the subjects with G/A mutation. (c) 2005 Elsevier B.V. All rights reserved.