Weanling male and female, stroke-prone, spontaneously hypertensive rats (SHR/SP) were fed: 1) regular commercial rat chow, 2) low protein fish diet, 3) low protein fish diet + 1% saline, 4) low protein animal diet, and 5) low protein animal diet + 1% saline. The blood pressure of all of the SHR/SP rose rapidly reaching 240 mmHg at 90 days of age; blood pressure of low protein fish diet + 1% saline-fed SHR/SP rose most rapidly, reaching levels ranging from 258 to 300 mmHg. All of these animals developed acute strokes by 90 days of age; none of the other diet-fed SHR/SP manifested cerebral damage. The protein poor diets prevented normal growth, caused hypogonadism, and severely reduced pituitary and adrenal gland weights. The low protein diets were stressful causing significantly increased secretion of adrenocorticotrophic hormone and marked increases in triglyceride, free fatty acid, cholesterol, glucose, and B.U.N. levels. The mixed hemorrhagic-thrombogenic cerebral lesions occurred ipsilaterally in the parietal lobe, involved basal ganglia, and appeared in areas of brain tissue nourished by the middle cerebral artery. It is concluded that the inclusion of 1% saline drinking water with a low protein diet of fish tissue origin specifically, was synergistic in enhancing the propensity of SHR/SP rats to develop their genetically-programmed hypertension and stroke.