SummaryOur data demonstrate the role, direct or indirect, of the peritubular oncotic pressure on Na reabsorption by the tubules of the canine kidney.The peritubular oncotic pressure is determined by two factors : i) the arterial plasma protein concentration and 2) the filtration fraction of the plasma in the glomeruli.Peritubular oncotic pressure was diminished by the reduction of plasma protein concentration without affecting the plasma volume (plasmapharesis) or by decreasing the filtration fraction (intrarenal infusions of acetylcholine), or by simultaneously reducing both parameters (systemic isotonic saline infusions). Conversely, peritubular oncotic pressure was risen by increasing the filtration fraction (systemic infusion of epinephrine) or the arterial plasma oncotic pressure (systemic or intrarenal infusions of albumin or of dextran).With any of the devices used, the decrease of the peritubular oncotic pressure leads to an increase of Na excretion rate which is due to a decreased Na reab-sorptive capacity of the tubules. Possible changes in glomerular filtration rate play only a secondary role, as is demonstrated by Na excretion rate-glomerular filtration rate covariancc analysis, as well as by the data obtained with progressive clamping of the aorta to assess quantitatively the influence of changes of filtered Na load on Na excretion rate. The natriuretic effect of the peritubular oncotic pressure decrement i sobscrved with constant (plasmapheresis, intrarenal infusion of acetylcholine) or increased (systemic isotonic saline infusion) plasma volume. The relationship between Na excretion rate and peritubular oncotic pressure is not affected by diuretic drugs (spironolactone, organomcrcui'ial compounds) which inhibit active Na transport by the tubuli.Inversely, increasing the peritubular oncotic pressure by injecting oncotically active substances or by increasing the filtration fraction leads to a decrease in Na excretion rate by enhancing tubular Na reabsorption. This effect is not influenced by changes in plasma or extracellular fluid volumes.In the experiments where the decrement in plasma protein concentration is counteracted by an increment in filtration fraction (in some plasmapheresis experiments), the peritubular oncotic pressure remains constant and Na excretion rate unaffected. Similarly, when the rise of the peritubular oncotic pressure induced by high dosages of albumin or of dextran is mitigated by a drop in filtration fraction (clue to increased renal blood flow), changes in Na excretion rate-arc insignificant.These results observed without any variation in plasma Na concentration, confirm the assumption formulated in the introduction : tubular Na reabsorption is governed, among others, by physical factors, oncotic and hydrostatic, probably operating at the basal membrane of the walls of the peritubular capillaries. The magnitude of the peritubular oncotic pressure integrates these oncotic and hydro-Static factors, since it depends both on plasma oncotic pressure and on filtration fraction, filtration fraction actually reflects the tonus of the efferent arterioles; change in this tonus induces a variation in the opposite direction in the hydrostatic-pressure within the peritubular capillaries.The fraction of reabsorbed Na which is regulated by the peritubular oncotic pressure amounts some 15 % of filtered Na load. Despite its quantitatively small participation in the total Na tubular transport, the peritubular oncotic pressure constitutes an automatically adjusted device which may correct, readily and without energy expenditure, Unbalanced hydromineral metabolism.