Plasma from 158 presumed healthy nuclear families has been analyzed by high-resolution, two-dimensional electrophoresis to study the frequency and effects of the genetic polymorphism in human apolipoprotein A-IV. Two common alleles, apo A-IV 1 and apo A-IV 2 were detected with relative frequencies of 0.943 and 0.057, respectively. Autosomal codominant transmission of these two alleles coded for by a single structural locus was demonstrated. Furthermore, we studied the effects of this apo A-IV variability on total plasma cholesterol, triglyceride, glucose levels and gamma-glutamyltransferase activity. Statistically significant differences among apo A-IV genotypes for the average glucose level were detected. The average effect of the apo A-IV 1 allele was to lower plasma glucose levels by 0.013 mmol/l, whereas the average effect of the apo A-IV 2 allele was to raise glucose levels by 0.213 mmol/l.