F rozen sections prepared from human aortic tissue containing fatty streak lesions were examined on a thermally controlled stage with a polarizing light microscope. Distinct birefringent droplets, 0.5-5 mum in diameter, were observed, many apparently aggregated into clusters. The clusters were about 20 X 20 mum in diameter (the approximate size of foam cells). Upon being heated, each smectic droplet exhibited a sudden change of birefringence, indicating a change of state. The transition temperatures were compared to assess compositional distributions in the tissue. We found that for 52% of the clusters the standard deviation of the cluster's droplet melting point distribution was less than half that observed in the surrounding microscopic field. If clusters were intracellular lipid inclusions, this observation indicates that the lipid composition within a foam cell is more homogeneous than that of the overall field. However, using statistical methods, we compared droplet melting populations from cluster to cluster and found significant heterogeneity. The observations can be interpreted to suggest that many foam cells modify the cholesteryl ester fatty acid composition of their accumulations be selective uptake, temporal sampling, or chemical reaction. Furthermore, the intercellular heterogeneity suggests that different cells in the lesion may have different metabolic and transport enzyme affinities or be in different states.