In the anesthetized dog, blood flow or metabolic rate was varied in kidney, hindlimb, or heart (experimental organ) while simultaneously diverting a portion of the venous outflow through forelimb or kidney (bioassay organ). The resistance to blood flow through the experimental organ gradually rose in the first few minutes following a large increase in flow and gradually fell following a large decrease in flow. Resistance to blood flow through an experimental organ (hindlimb) fell following increase in metabolic rate. In each case, bioassay organ resistance changed in the same direction when the assay organ was the forelimb and in the opposite direction when the assay organ was the kidney. These findings suggest that active hyperemia, reactive hyperemia, and autoregulation of blood flow result, at least in part, from alteration in the chemical environment of the blood vessels. Other findings in this study support the possibility that adenosine triphosphate contributes to the change in environment.