We tested the hypothesis that modest, overfeeding-induced weight gain would increase sympathetic neural activity in nonobese humans. Twelve healthy males (23±2 years; BMI, 23.8±0.7) were overfed approximately 1000 kcals/day until a 5 kg weight gain was achieved. Muscle sympathetic nerve activity (microneurography), resting blood pressure, body composition (dual energy x-ray absorptiometry) and abdominal fat distribution (computed tomography) were measured at baseline and following four weeks of weight stability at each individual's elevated body weight. Overfeeding increased body weight (73.5±3.1 vs. 78.4±3.2 kg, P<0.001) and body fat (14.9±1.2 vs. 18±1.1 kg, P<0.001) in 42±8 days. Total abdominal fat increased (220±22 vs. 266±22 cm², P<0.001) with weight gain, due to increases in both subcutaneous (158±15 vs. 187±12 cm², P<0.001) and visceral fat (63±8 vs. 79±12 cm², P=0.004). As hypothesized, weight gain elicited increases in sympathetic burst frequency (32±2 vs 38±2 burst/min, P=0.002) and burst incidence (52±4 vs. 59±3 bursts/100 heart beats, P=0.026). Systolic, but not diastolic blood pressure increased significantly with weight gain. The change in burst frequency was correlated with the percent increase in body weight (r=0.59, P=0.022), change in body fat (r=0.52, P=0.043) and percent change in body fat (r=0.51, P=0.045). The results of the current study indicate that modest diet-induced weight gain elicits sympathetic neural activation in nonobese males. These findings may have important implications for understanding the link between obesity and hypertension.