Involvement of sympathetic nervous system and natriuretic peptides in the control of exercise-induced lipid mobilization was compared in overweight and lean men. Lipid mobilization was determined using local microdialysis during exercise. Subjects performed 35-min exercise bouts at 60% of their maximal oxygen consumption under placebo or after oral tertatolol (a beta-adrenergic receptor (AR) antagonist). Under placebo, exercise increased dialysate glycerol concentration (DGC) in both groups. Phentolamine (alpha-AR antagonist) potentiated exercise-induced lipolysis in overweight but not in lean subjects; the alpha2-antilipolytic effect was only functional in overweight men. After tertatolol administration, the DGC increased similarly during exercise whatever the probe in both groups. Compared to the control probe under placebo, lipolysis was reduced in lean but not in overweight men treated with the beta-AR blocker. Tertatolol reduced plasma NEFA and insulin concentration in both groups at rest. Under placebo or tertatolol, the exercise-induced changes in plasma NEFA, glycerol and insulin concentrations were similar in both groups. Exercise promoted a higher increase in catecholamine and ANP plasma levels after tertatolol administration. In conclusion, the major finding of our study is that in overweight men, in addition to an increased alpha2-antilipolytic effect, the lipid mobilization in SCAT that persists during exercise under beta-blockade is not dependent on catecholamine action. It is related to a concomitant exercise-induced rise in plasma ANP when exercise is performed under tertatolol intake and a decrease in plasma insulin.