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S tudies of adipose tissue cellularity were carried out in a group of nonobese adult male volunteers who gained 15-25% of their body weight as the result of prolonged high caloric intake. Adipose cell size (lipid content per cell) was determined in tissue obtained from three subcutaneous sites (gluteal, anterior abdominal wall, and triceps) and total adipose cell number estimated from measurement of total body fat.Five experimental subjects gained an average of 16.2 kg of body weight, of which 10.4 kg was determined to be fat. Expansion of the adipose mass was accompanied by a significant and relatively uniform increase in fat cell size in each subcutaneous site tested. Total adipose cell number did not change as a result of weight gain and expansion of the adipose depot in adult life. Subsequent loss of weight and restoration of original body fat was associated with a reduction in adipose cell size at each subcutaneous site, but no change in total number. In two control subjects who neither gained nor lost weight there were no changes in total adipose cell number or cell size. These observations suggest that expansion and retraction of the adipose depot in adult life is accompanied by changes in adipose cell size only.Significant differences in both the size and total number of adipose cells were observed between subjects in both the experimental and control groups. In addition, within individuals of both groups there were significant differences in cell size when adipose cells from the three subcutaneous sites were compared. These findings indicate that wide variations in adipose cell size and number exist in nonobese individuals having similar adipose depot sizes.