Abstract Within the frame of reference of possible relationships between history of carcinoma, low serum cholesterol, and/or high fecal cholesterol, and keeping in mind familial aggregation of plasma cholesterols and lipoprotein cholesterols, the purpose of this report was to assess relationships of parental mortality and longevity to cancer and coronary heart disease risk factors (cholesterol and lipoprotein cholesterols) in their adult progeny, utilizing the cross-sectional Cincinnati Lipid Research Clinic's Prevalence Study. Multivariate analysis of covariance was used to assess the effect of parental cause of death, if dead, and parental longevity, if alive, for plasma total cholesterol, triglyceride, high- and low-density lipoprotein cholesterol (C-HDL, C-LDL), of their adult progeny. The age, sex, race, cigarette use, alcoholic beverage consumption, dietary saturated fat and cholesterol intakes, recall group, and Quetelet index of the offspring served as covariables, the mothers' and fathers' “death” outcome served as classification variables. Family history was available on 1,702 parents (851 fathers, 851 mothers) of 851 adult offspring. There were several significant parental mortality history: covariable interactions for progeny's plasma cholesterol, C-HDL, and C-LDL. When progeny's dietary cholesterol intake increased, C-LDL fell in progeny whose mothers had lethal carcinoma and rose in those whose mothers had lethal coronary heart disease. As dietary cholesterol increased, C-HDL fell in progeny whose fathers had lethal cancer, and rose in those whose fathers were alive and older than age 75 years. As wine intake increased, C-HDL of progeny whose fathers had lethal cancer rose most markedly, while the C-LDL of progeny whose fathers had lethal cancer fell. Similarly, as mixed alcoholic beverage intake increased, C-HDL levels rose and C-LDL levels fell appreciably in progeny whose mothers and/or fathers had lethal carcinoma. Black progeny whose fathers had lethal carcinoma had low total cholesterol and C-LDL levels when compared with whites. These significant interactions of parental mortality history for their adult progeny's cancer and coronary heart disease risk factors (cholesterol and lipoprotein cholesterols) suggest that familial aggregations of risk factors for both cancer and coronary heart disease appear to involve plasma cholesterol, C-LDL, and C-HDL. Currently, the significant interactions and associations observed in this study cannot be equated with causal relationships. However, these interactions present hypotheses for further longitudinal assessment and substantiation which might explicate causal relationships.