Rapid injection of 40 ml. of 5 per cent saline into the femoral or brachial arteries of 24 dogs resulted in an average elevation of arterial blood pressure of +42/+20 mm. Hg, an increase in the heart rate of +20 beats/min., and an acceleration of the respiratory rate of +140 per cent. The response began 6 to 10 seconds after the onset of injection and lasted for 5 to 30 minutes. It occurred with the injection of hypertonic solution of saline, dextrose, and urea. The magnitude of the response was related to the degree of hypertonicity. Responses could be provoked by 10 ml. of 1.25 per cent saline. Rapid intra-arterial injection of isotonic saline, dextrose, and urea solutions, and of whole blood in volumes up to 80 ml. had no circulatory effect. Rapid injection of distilled water, 0.225 per cent and 0.45 per cent saline into the femoral or brachial arteries resulted in a slight degree of hypotension and a rise in the respiratory rate. The appearance of circulating catechol amines following the response to intra-arterial injection of hypertonic solutions was suggested by the demonstration of hypotensive response to intravenous injection of phentolamine. These responses to injection of hypertonic and hypotonic solutions in the femoral artery were abolished by section of the sciatic nerve in animals with an ipsilateral partially-transected hind limb, a preparation which left intact only the femoral artery, femoral vein, and femur. Sciatic section in the intact limb reduced but did not abolish the response. Removal of the sympathetic chain from the eleventh thoracic through the third lumbar ganglia had no apparent effect. It is concluded that the response to femoral aud brachial intra-arterial injection of hypertonic and hypotonic solutions is initiated by peripherally located “osmoreceptors” in the distribution of these arteries and is mediated via a reflex whose afferent fibers travel in the peripheral somatic nerves and enter the spinal cord without passing through the sympathetic chain. The efferent are is the sympathetic nervous system.