Because of its association with longevity and reduced incidence of coronary heart disease, it becomes important to find out how elevated HDL-cholesterol levels are determined. Analyses of family data from Cincinnati initially suggested environmental factors common to sibs; however, some form of dominant inheritance could not be ruled out. Reanalysis of the Cincinnati data by Iselius and Lalouel concluded against a major locus, but did identify three families as possibly segregating for a major locus. Analysis of an additional 26 kindreds from the same population in Cincinnati by Siervogel and associates concluded that a major gene could be causing familial aggregation of high density lipoprotein in white kindreds. In this analysis, we pooled all the white Cincinnati kindreds (n = 31), and investigated the familial transmission using complex segregation analysis. We failed to obtain clear evidence for major locus determination. Under the parsimonious hypothesis of no major locus, the polygenic heritability and common sibling environmental correlation were estimated as 0.531 and 0.263, respectively, consistent with other evidence.