Upper-body obesity (UB Ob) is more strongly associated with adverse health consequences; however, few obesity-treatment studies have examined outcome according to body-fat distribution. To examine whether diet and formal- or informal-exercise instruction causes differential changes in health and lipid profiles, ten LB Ob and nine UB Ob premenopausal women received dietary intervention (2.1 MJ-deficit/d for 16 wk) and were randomly assigned to either formal- or informal-exercise instruction. Weight loss was similar between groups (approximately 8 kg), and no change occurred in lean body mass or basal metabolic rate. Baseline cholesterol and triglycerides were greater (P < 0.01) in UB Ob than LB Ob women and decreased more (P < 0.01) in response to treatment in UB Ob women. Formal exercise instruction increased high-density-lipoprotein cholesterol (P < 0.05) especially in UB Ob women. Future studies on treatment of obesity should include consideration of regional fat distribution.