Apolipoprotein (apo)H (also known as beta 2 glycoprotein-I) is a glycoprotein synthesized by liver cells and it is present in the blood associated with plasma lipoproteins. APOH displays a genetically determined structural polymorphism: three alleles (APOH*1, APOH*2, APOH*3) at a single locus on chromosome 17 code for different isoforms, and population studies have shown that APOH*2 is the most frequent allele. This paper assesses the relation between APOH phenotypes and plasma apoH levels in a population composed of 278 healthy subjects (243 H2/2, 32 H3/2, 2 H3/3, 1 H2/1; allele frequencies APOH*1 0.002, APOH*2 0.934, APOH*3 0.064) and 245 diabetics (212 H2/2, 30 H3/2, 3 H3/3; allele frequencies APOH*2 0.927 and APOH*3 0.073). Determination of apoH levels by competitive ELISA gave a mean value of 26.3 +/- 9.8 mg/dl for all subjects, 22.6 +/- 7.7 in normals vs 30.6 +/- 10.3 in diabetics (p = 0.0001), and 23.0 +/- 7.9, 19.3 +/- 5.4 and 18.5 +/- 3.5 mg/dl for H2/2, H3/2 and H3/3 in normals and 31.1 +/- 10.1, 28.2 +/- 10.8 and 15.7 +/- 9.0 mg/dl in diabetics, respectively. ANCOVA of the adjusted data revealed a significant difference in apoH levels for the three phenotypes in both the normal subjects (p = 0.01) and the diabetics (p = 0.02). ANCOVA of the whole samples of subjects, controlling for diabetes as well as age, sex and total cholesterol, indicated a substantial effect of phenotype, independent of the other variables (p = 0.0007).