Guanethidine was administered to 10 normal subjects in order to examine the effects of reduced adrenergic function on plasma volume. An increase in the plasma volume was observed averaging 21.4% after 1 week, and 12.1% and 13.1% after 2 and 3 weeks of drug administration. A similar change in plasma volume resulted when alphaadrenergic blockade was produced with phenoxybenzamine. These changes occurred in the absence of sodium retention and were associated with attenuation of forearm venous sympathetic reflexes and a rise in forearm venous compliance. The increase in venous compliance which was observed was proportional to the changes in plasma volume in these subjects. Thus, the sympathetic nervous system through its control of venous resistance may provide a means whereby the blood volume can be regulated.