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Current interest in lipoprotein deficiency states stems from the growing realization of their importance in the etiology of premature coronary heart disease. While hypercholesterolemia and coronary heart disease risk are strongly correlated in their etiologic relationship, it is becoming equally clear that deficiencies in HDL, whether congenital or acquired, also enhance the risk for the future development of coronary atherosclerosis. This has led to renewed attention to the lipid hypothesis and realization of the fact that each lipoprotein class and apoprotein species has specific functions in the transport and cellular uptake of various lipids. It is a truism that a biochemical correlate of disease once identified is subsequently recognized with increasing frequency in clinical medicine. The story of HDL was no exception. Indeed hypoalphalipoproteinemia appears to be a disease of high prevalence approaching and perhaps even exceeding that of familial hypercholesterolemia. Its clinical signifi- cance escaped our notice for many years largely due to a heavy emphasis on hypercholesterolemia and to difficulties in measuring HDL reliably.