The effects of prostaglandin F2 alpha on renal function were studied in hydropenic dogs. Peak responses occurred in 45 to 60 min. PGF 2 alpha (0.3 microgram.kg-1.min-1) increased urine flow by 1.3 +/- 0.3 ml/min and increased sodium excretion by 27.1 +/- 4.6 microEq/min. Papillary nonurea solute concentration was decreased from 981 +/- 153 to 347 +/- 58 mOsm/kg of H2O and the corticomedullary urea gradient was abolished. Although renal blood flow, glomerular filtration rate, peritubule capillary hydrostatic pressure and renal venous pressure were not changed by PGF2 alpha, urine from the infused kidney became distinctly hypotonic. A "washout" of medullary solutes was not supported by the data since the volume of distribution of 125I-albumin, an index of papillary perfusion rate, was not changed by PGF2 alpha. The contribution of decreased salt reabsorption from Henle's loop was evaluated in dogs that received furosemide and produced essentially isotonic urine. Subsequent intrarenal PGF2 alpha, increased CH2O and produced hypotonic urine with no significant further change in UNaV. These studies suggest that inhibition by PGF2 alpha of salt reabsorption from the thick ascending limb of Henle's loop may account for the modest natriuretic effect and contribute to the dissipation of the nonurea solute gradient. Additionally, there is an inhibition of both vasopressin-mediated water and urea reabsorption which contributed to the diuretic and hyposthenuric effects of infused prostaglandins.