Effects of protein malnutrition on adipose tissue development were studied in weanling male Sprague-Dawley rats fed isocaloric diets ad libitum containing either 22% (controls) or 8% (protein-malnourished rats) casein, and in rats pair-fed to the protein-malnourished rats with the 22% casein diet. After 32 days on the diet, protein-malnourished rats were 37% and pair-fed 67% the weight of the controls, while torso length was 37% and 73% of controls, respectively. Food consumption relative to body weight was greatest in protein-malnourished rats. Compared to control rats, the distal epididymal adipocyte number in the protein-malnourished rats was decreased in proportion to the decrease in body size and was more closely related to the protein intake than to the total calories consumed. After 32 days on diet, mean adipocyte number per 2 distal pads was 11.7 x 10(6) in controls and 4.3 x 10(6) in protein-malnourished rats. In pair-fed rats, cell number lagged behind controls at 4 and 11 days, but was normal at 32 days (11.4 x 10(6) cells). The distal epididymal pad adipocyte size and percent lipid were similar in all groups during the first 25 days of dietary treatment. Adipocyte size was increased significantly in controls at day 32 compared to the other two groups. At each time studied through day 25 on diet, epididymal pad weight was related to the adipose cell number rather than the cell size. It is concluded that severe restriction of dietary protein during the postweaning period of growth in rats results in decreased epididymal adipocyte proliferation and/or differentiation concomitant with generalized growth retardation, whereas isocaloric feeding of a diet of normal protein content is associated with only a transient delay in adipose tissue development.