Aim To elucidate the relationship between the apolipoproteins,especially apoA-I and the alteration of HDL subclasses in type Ⅱa and Ⅱb hyperlipidemic subjects.Methods Apolipoprotein(apo) A-I contents of serum HDL subclasses in 68 type Ⅱa and 67 type Ⅱb hyperlipidemic subjects and 233 normal controls were determined by two-dimensional gel electrophoresis coupled with immunodetection method.Results Compared with normal controls,the contents of small-sized preβ1-HDL,HDL3b and HDL3a were significantly higher(P<0.01),but those of large-sized HDL2a and HDL2b were significantly lower(P<0.01 or P<0.05) in type Ⅱa and Ⅱb hyperlipidemic subjects.In addition,preβ1-HDL and HDL3a increased significantly(P<0.05) while HDL2a and HDL2b decreased significantly(P<0.01) in type Ⅱb versus type Ⅱa hyperlipidemic subjects.Both in type Ⅱa and Ⅱb hyperlipidemic group,compared to the subjects with high apo A-I levels,all small-sized HDL subclasses(except preβ2-HDL)increased significantly(P<0.01 or P<0.05) while large-sized decreased significantly(P<0.01) in the subjects with low apo A-I levels.Correlation between HDL subclasses and apolipoproteins showed that apoA-I was positively and significantly correlated with all HDL subclasses(P<0.01).In contrast,concentrations of apoB100,apoCⅢ showed positive and significant correlation with small-sized preβ1-HDL while negative and significant correlation with large-sized HDL2a and HDL2b.Conclusions The particle size of HDL shifted towards smaller size in type Ⅱa and Ⅱb hyperlipidemic subjects,and the shift was more prominent in type Ⅱb hyperlipidemic subjects.Apolipoprotein levels,especially apoA-I level influence the distributions of HDL subclasses in type Ⅱa and Ⅱb hyperlipidemic subjects.