The present study compares plasma norepinephrine (PNE), renin activity (PRA), aldosterone (PA), and insulin (RIAI) levels between 13 normotensive and 42 hypertensive obese subjects during weight maintenance, and in 19 of the 42 obese hypertensive subjects, these variables were measured during 16 weeks on a very low calorie diet (VLCD). Mean values for baseline RIAI and PNE were elevated in the 55 obese subjects compared to nonobese controls. However, when the normotensive and hypertensive groups were compared, mean values for PNE, PRA, PA, and RIAI were not different. In the 19 obese hypertensive subjects studied on the VLCD, there were significant reductions from baseline in mean body weight, blood pressure, RIAI, and PNE, but not for PRA or PA. Two phases of blood pressure, RAIA, and PNE responses to weight loss were noted. In the early phase (days 1-7), blood pressure and RAIA decreased dramatically, whereas PNE, PRA, and PA increased. During the late phase (weeks 2-16), further significant decreases in blood pressure and weight were accompanied by reductions in PNE (604 +/- 50 to 403 +/- 43 pg/mL, P < .01) and in RIAI (13.9 +/- 1.7 to 10.3 +/- 1.6 microU/mL, P < .05). As levels of insulin and norepinephrine were similar in normotensive and hypertensive obese individuals during weight maintenance, they may not contribute to the hypertension associated with obesity. During weight loss, however, the temporal changes in blood pressure, insulin, and norepinephrine suggest their mediation of the hypotensive response.