We have studied 32 kindreds identified by propositi with primary type V hyperlipoproteinemia. The clinical presentation, metabolic associations, and natural history confirm the distinctiveness of primary type V hyperlipoproteinemia from other lipoprotein abnormalities. Although the underlying defect(s) remains unknown, several factors such as obesity, alcohol, drugs, and diet are able to modify the glyceridemia, the major manifestation of this disorder. Abnormalities of postheparin lipolytic activity or its subfractions do not appear to be involved in the pathogenesis of primary type V. The prevalence of hyperuricemia, diabetes, pancreatitis, and xanthomatosis appears high among the 32 propositi; the last two entities are much less prevalent in the relatives, even among those relatives classified as hyperglyceridemic. There is no evidence in these families of excessive coronary artery disease prevalence. Triglyceride levels are positively associated with age in this population, especially among women. Average triglyceride levels were lower for women than for men before age 50.