The influence of dietary sodium chloride on the urinary excretion of prostaglandins (PGs) was studied in unanesthetized female rabbits housed in metabolic cages. Urinary PG levels were determined by radioimmunoassay, bioassay and gas chromatography-mass spectrometry. In the first experiment rabbits were fed at high (2.5%) and later a low (0.25%) sodium chloride diet ad libitum. A 2--5 fold increase in excretion of immunoreactive PGF2alpha (iPGF2alpha) and iPGE2 was noticed when animals were given the low salt diet. Since it could not be excluded that dietary factors other than sodium chloride contributed to the changes a second, more controlled experiment was undertaken. Rabbits were fed 30 g/kg per day of diets offering only in the content of sodium chloride, 2% and 0.37% respectively. On the high salt diet the rabbits excreted 0.1 +/- 0.04 microgram/day of PGE2 and 2.0 +/- 0.5 microgram/day of iPGF2alpha. After equilibration on the low salt diet the PGE2 excretion rate increased to 1.5 +/- 0.3 microgram/day (p less than 0.001) and that of iPGF2alpha to 3.4 +/- 0.4 microgram/day (p less than 0.01). These results thus point to an inverse relationship between renal sodium excretion and the activity of the renal prostaglandin system.