Blood pressure, forearm hemodynamic data, and red blood cell (RBC) cation transport measurements were obtained in 27 men with body mass indexes (BMI) greater than 26.6 kg/m2 and 21 men with BMI less than 26.6 kg/m2. Subjects with higher BMI had significantly higher systolic and diastolic pressure measured both noninvasively and invasively, P less than .02-.001. Baseline forearm blood flow (FABF) was substantially higher in the heavier subjects, P less than .02, whereas forearm vascular resistance (FAVR) levels were not different, P greater than .10. Despite the higher baseline forearm blood flow, the high BMI group displayed a greater rise in flow, P less than .01, in response to a regional phentolamine infusion, an index of vascular alpha-tone. Results of multiple regression analysis suggested that overweight was indirectly correlated with vascular alpha-tone via a relationship with arterial plasma norepinephrine concentration, a marker of sympathetic drive, and bumetanide-sensitive RBC Na+-K+ cotransport activity. These data indicate that in overweight men (1) higher FABF is not fully counter-balanced by lower FAVR; (2) increased vascular alpha-tone contributes to the altered flow-resistance relationship and thereby to the elevated blood pressure; and (3) greater sympathetic drive and Na+-K+ cotransport activity may explain the elevated vascular alpha-tone.