Adipocyte triglyceride, cholesterol, and tocopherol contents were examined in three human obese subjects, all over 150% of ideal weight, who were placed on weight reduction formula diets for 11, 21, and 25 wk, respectively. Body weight decreased from 77 to 63 kg, 188 to 147 kg, and 147 to 99 kg, respectively. All subjects had normal serum cholesterol and triglyceride levels, and these did not vary greatly during weight reduction. Subcutaneous fat was obtained at frequent intervals by needle aspiration from the buttocks before and during weight reduction. Adipocyte size was measured by osmium tetroxide fixation technique, tissue cholesterol content by GLC, tissue triglyceride content by lipid extraction, and tissue tocopherol by thin-layer chromatography. Initial adipocyte size was 0.54, 1.06, and 0.96 micrograms of lipid per cell, respectively (normal 0.60), and the mean cell size decrease during weight reduction was 40%, all due to triglyceride mobilization. Adipocyte cholesterol and tocopherol content did not change significantly during weight reduction. These data are consistent with the concepts that triglycerides but not cholesterol or tocopherol are mobilized from the fat cell during up to 6 months of weight reduction and that independent mechanisms control the efflux of these adipocyte constituents.