Plasma volume (PV) and red blood cells volume (RBCV) were measured in 76 normotensive acromegalic patients (42 males and 34 females) and compared with those of 28 controls on the basis of body surface. In untreated males PV and RBCV were significantly higher than in normals (P less than 0.001) and total blood volume (TBV) was above the normal range in 85%. Untreated females also showed an elevated PV but had significantly lower RBCV than the male patients. The only vascular volume of the patients with correlated significantly with the body weight or surface was RBCV in females. One to five studies were done after treatment in 52 patients and analyzed as a function of plasma GH levels. Plasma volume reverted to the normal range (males) or was significantly lower than in untreated patients (females) in the groups of patients with normal GH levels while RBCV normalized at higher GH concentrations. At similar GH levels, treated patients without pituitary failure (n = 35) or given T4 and/or cortisol substitution for hypopituitarism showed similar vascular volumes. The plasma volume and TBV in both sexes and RBCV in males was significantly correlated with Log 10 GH levels. It is concluded from these data and other experimental evidence that endogenous GH hypersecretion is responsible for the reversible PV and RBCV increases frequently found in acromegalic patients.