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The level of renal fatty acid binding protein (FABP) was quantified by a specific radial immunodiffusion method using an antibody to cytosolic FABP in stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) at 5, 10, 20 and 40 weeks of age. Increased levels were found in the SHRSP medulla, but not in the WKY medulla. The increase occurred in the hypertension development period, reaching a peak at 20 weeks of age. This increase was confirmed by immunoblotting. There was no significant change of FABP in the cortex. To elucidate the mechanism responsible for these changes in the FABP level, three antihypertensive drugs (nicardipine, hydralazine and enalapril) were given to SHRSP at 20 weeks of age for a period of four weeks. Antihypertensive treatment significantly inhibited the development of hypertension and the increase in the medullary FABP level. The differential response of FABP in SHRSP and WKY suggests that this protein may play an important role in the cellular metabolism of fatty acids under the pathological condition of high blood pressure.