Steinberg and colleagues have previously described a unique kindred with normotriglyceridemic hypobetalipoproteinemia (1979. J. Clin. Invest. 64:292-301). In a reexamination of this kindred, we found an abnormal apolipoprotein (apo) B species, apo B-37 (203,000 mol wt), in the plasma lipoproteins of multiple members of the kindred. In affected individuals apo B-37 was found in very low density lipoproteins, along with the normal apo B species, apo B-100 and apo B-48. High density lipoproteins (HDL) also contained apo B-37, but no other apo B species. The first 13 amino-terminal amino acids of apo B-37 were identical to those of normal apo B-100. We utilized a panel of 18 different apo B-specific monoclonal antibodies and polyclonal antisera specific for apo B-37 and the thrombin cleavage products of apo B-100 to map apo B-37 in relation to apo B-100, apo B-48, and the thrombin cleavage products of apo B-100. The results of those immunochemical studies indicated that apo B-37 contains only amino-terminal domains of apo B-100. In affected individuals, the majority of apo B-37 in plasma was contained in the HDL density fraction. Within that fraction apo B-37 was found on discrete lipoprotein particles, termed Lp-B37, that had properties distinct from normal HDL particles containing apo A-I. This report documents for the first time the existence of an abnormal apo B species in humans. Further study of apo B-37 and lipoprotein particles containing apo B-37 should lead to an improved understanding of apo B structure and function.