This study examined the effect of weight loss (separate from energy restriction) and weight maintenance/rebound over time on blood pressure, serum lipids, and body composition in 24 obese (mean 137% ideal body weight (IBW)) females with mild to moderate hypertension. Weight loss was induced under tightly controlled General Clinical Research Center conditions until each subject had lost at least 10 kg (mean 13 kg) and attained normal body weight (< 120% IBW). After 4 years subjects returned for repeat evaluation. Weight changes were compared with 24 pair-matched normal weight controls who were also followed for 4 years. With weight loss, significant improvements were seen in standing mean arterial pressure (MAP), serum total cholesterol, low-density lipoprotein cholesterol, and triglycerides. Subjects regained 11 kg (87% of the weight lost) over the 4 year follow-up period while control subjects gained only 2 kg. Subjects who chose self-selected exercise gained less weight than nonexercisers (6 kg vs. 13 kg, P < 0.05). With weight regain there were significant increases in standing and supine MAP, total cholesterol, and high-density lipoprotein (HDL) cholesterol. The amount of weight regained was significantly correlated with standing MAP (r = 0.73), triglycerides (r = 0.43), and HDL cholesterol (r = -0.47). The percentage fat of the weight regained was no greater than that of the weight previously lost. Weight loss, distinct from energy restriction, was associated with improvements in blood pressure and serum lipid levels. The ability to sustain these improvements in the co-morbidities of obesity was directly related to the persistence and magnitude of weight loss maintenance.