The authors have induced experimentally middle-ear effusions and cholesterol granulomas one month and later after tubal obstruction in squirrel monkeys. Cholesterol crystallization has occurred frequently in the middle-ear fluids of three-and six-month-animals, and, typical cholesterol granulomas were noted in four of the eight middle ears of six-month-monkeys. The shape and size of the cholesterol crystals were variable, depending upon the surrounding cells of fluid. In middle-ear effusion, the crystals formed rather large rectangular structures, which tended to become smaller and thinner, as the granulomas developed. The granuloma containing cholesterol crystals was rich in various oxidative and hydrolytic enzymes. The large cells surrounding the crystals show intense-to-strong enzyme activity and probably play a phagocytic role in the developing and healing processes of the granuloma.