The polyuria and hyposthenuria noted particularly following blood transfusion after prolonged periods of hypotension (dog, monkey) seem best explained by a prostaglandin-antidiuretic hormone (PG-ADH) antagonism, operating primarily in the renal medulla. The kidney releases greatly enhanced amounts of PGE at this time, which probably act primarily in the renal medulla, then secondarily influence the systemic (arterial) levels by passing in greater amounts through the lungs. The lungs normally metabolize the major portion of PGs delivered to them. Our data suggest impairment of the lung's "up-take-metabolizing" mechanism, but also could be interpreted as involving enhanced release of PGE from the lung, so net pulmonary extraction, (V--A)/V, shifts from positive to zero or even negative values in the hypotensive shock phase. This ratio tends to improve after transfusion, but systemic PGE levels remain elevated. It is speculated that in hemorrhagic shock enhanced concentration of PGE and other vasodilator PGs, produced in increased amounts by the kidney (and possibly other organs and tissues), appear in greater amounts in the systemic plasma because of the lung's altered function. These exert a decompensatory action on the peripheral vasculature.