The principal site of action of intravenous regional anesthesia was studied using both prilocaine HC1 0.5% and technetium pertechnetate to define their distribution in the upper limb during this method of anesthesia. Using a single upper arm tourniquet and injecting technetium pertechnetate into a cubital fossa vein, the isotope spread to the finger tips. When a double tourniquet system was used to isolate the hand from the forearm, the following results were obtained: for up to 20 min after injection of the 40 ml of normal saline and radioisotope there was no leakage into the general circulation nor into the hand; after injection of 40 ml prilocaine HCl 0.5% into a cubital fossa vein, there was no anesthesia in the hand except for a small area on the dorsum corresponding to the area of sensory distribution of the radial nerve; while the tourniquets were inflated there was cramping pain in the hand. The results indicate that the initial analgesia obtained with the intravenous regional technique was due to blockade of small nerves or possibly nerve endings and not of the major nerve trunks at the elbow as has been suggested previously.