The lipid state hypothesis proposes that liquid crystalline states of cholesteryl esters play a role in the development and persistence of the fatty streak lesions characteristic of atherosclerosis. We have tested several corollaries suggested by this hypothesis and find that the ensemble of droplets in atherosclerotic tissue are predominantly in the isotropic (fluid) state at 37.0 degrees C. Furthermore, the liquid-crystalline state transition behavior of these droplets is not influenced significantly by the distribution of component cholesteryl ester species. There are no significant correlations between the transition behavior of the droplets and the age, sex, or race of the subjects from which tissue samples were taken. These results show that the lipid state hypothesis is weak, and that the origin and persistence of fatty streak lesions in humans is probably dominated by other factors.