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1. We have studied the effects of two prostaglandin synthesis inhibitors on renal cortical blood flow distribution in conscious rabbits. 2. Renal blood flow distribution was estimated by means of radioactive microspheres injected into chronically implanted left atrial cannulae. Cardiac output was measured by a thermodilution technique. 3. Measurements were made in groups of animals treated with either indomethacin, meclofenamate or control injections of phosphate buffer. 4. A method of microtome slicing of the renal cortex was developed to standardize measurements. Microtome sections were grouped into inner, middle and outer zones. After both indomethacin and meclofenamate there was a reduction in total renal blood flow with a redistribution of flow from inner to outer cortex. 5. Estimated renal vascular resistance rose in all three cortical zones. 6. The data support the hypothesis that renal prostaglandin synthesis is necessary for maintaining flow to the deep cortex. It is suggested that renal prostaglandins may also influence flow in more superficial zones. 7. Estimated total systemic vascular resistance was increased both with meclofenamate and indomethacin, suggesting an inhibiting effect of prostaglandins on arteriolar tone throughout a major part of the systemic circulartion.