Comparative localization of apolipoproteins (apo) B and A in small, raised fibrolipid lesions was performed to determine whether low density lipoproteins (LDL) and high density lipoproteins (HDL) may be involved in the formation of the earliest identifiable lipid-rich core regions found in atherosclerotic fibrous plaques. Apo B was observed associated with the superficial layer of foam cells in collagenous areas of the lesion cap and within the lipid-rich core region. The lipid-rich core region was well-circumscribed by an intense band of apo B staining along both luminal and medial aspects. Apo A staining was confined to the noncellular elements of the fibrolipid lesion. Collagenous areas were speckled with fine, punctate granules of immunoreactive apo A. A homogeneous, granular apo A staining pattern was characteristic throughout the core region. With these data from a relatively early lesion in the development of the atherosclerotic fibrous plaque, we conclude that: 1) both LDL and HDL can accumulate in the lipid-rich core region since no preferential staining for apo B over apo A was observed in this region, and 2) the paucity of cell-associated apo A staining in small fibrolipid lesions suggests that HDL interacts with the arterial wall differently than does HDL.