Two-locus and bivariate segregation analyses of HDL-C and apo AI were carried out using the GAW8 Berkeley data set. For HDL-C, results are ambiguous. Both the mixed environmental model and the mixed Mendelian model fit the data equally well. For apo AI, however, univariate one-locus segregation analysis suggests a Mendelian major gene controlling its levels. Moreover, two-locus analysis suggests a second major gene is involved. Bivariate segregation analysis indicates these data cannot resolve the question as to whether a single Mendelian major gene with pleiotropic effects controls levels of both HDL-C and apo AI in humans.