Cells of the U937 cell line were grown in delipidated calf serum for 24 and 48 hr. These cells are known cholesterol auxotrophs. When grown for 48 hr without an exogenous source of cholesterol, these cells are known to become depleted of their intracellular cholesterol stores by greater than 95%. The result is an aggregation of the cells upon mild agitation of the culture. Examination of the cell aggregate from these cultures revealed cells in various stages of altered morphology. There was a loss of microvilli from the cells. Subsequently, the Golgi complex became dilated, and secondary lysosomes and myelin figures accumulated in the cytoplasm. The cells became swollen, and the rough endoplasmic reticulum became dilated. A small percentage of the cells showed complete disintegration, with release of membrane-bound fragments and other intercellular debris. These events suggest that the depletion of cholesterol results in the inability of the cell to produce usable membrane. As a consequence, the synthetic apparatus of the cell becomes disrupted.