In a search for the role of long-term hypocaloric feeding on the expression of the erythrocyte Na pump in obesity, we examined three groups of subjects. Group 1 consisted of 10 obese subjects who had been under treatment for a long period of time with a very-low-calorie diet (500 kcal/d) while group 2 consisted of 10 age-, sex-, and body mass index-matched obese subjects on their usual diet; in the third group, 12 normal-weight subjects on a free diet served as controls. There was no difference between the groups in the number of erythrocyte binding sites per cell. On the contrary, the Na-K-ATPase activity was significantly lower in the obese group 1 (0.35 +/- 0.09 mumol Pi x mg protein-1 x h-1) compared to that observed in the obese group 2 (0.42 +/- 0.07, P less than .05) and in control subjects (0.45 +/- 0.06, P less than .05). Sex, duration of hypocaloric feeding, and the amount of weight loss before the study in the obese group 1 seemed not to be related to the Na pump parameters. We conclude that long-term severe hypocaloric feeding may be a factor in altered erythrocyte Na-K-ATPase in obese individuals.