1. Heart mass, prolyl endopeptidase activity and fractionated proteins from heart tissue were studied in one-kidney, one clip hypertensive rats (N = 6) and compared to sham-operated rats (N = 6). 2. Body weight, arterial pressure and tissue mass were measured 4 weeks after artery clipping. Z-Gly-Pro-p-nitroaniline hydrolysis was used to measure tissue prolyl endopeptidase activity in the homogenate. Protein was fractionated into the soluble and myofibrillar fractions. 3. In the normotensive rats, prolyl endopeptidase activity expressed in terms of protein specific activity (microM substrate hydrolyzed h-1 mg supernatant protein-1) occurred in atria and was 2.5-fold higher than in the ventricles (3.79 +/- 0.20 vs 1.44 +/- 0.02, P < 0.05). In the one-kidney, one clip hypertensive rats, the left ventricle tissue increased 1.7-fold (2.27 +/- 0.11 vs 3.72 +/- 0.11 mg wet weight tissue/g body weight, P < 0.001), the soluble protein fraction (54.86 +/- 3.60 vs 57.38 +/- 6.64 mg/g wet weight tissue) was unchanged, while the myofibrillar fraction increased 1.9-fold (118.9 +/- 9.09 vs 229.8 +/- 8.47 mg/g wet weight tissue, P < 0.001). 4. The specific activity of the atrial and ventricular prolyl endopeptidase decreased in atria and increased in ventricles as the result of hypertension (3.79 +/- 0.2 vs 2.84 +/- 0.13 and 1.44 +/- 0.02 vs 1.87 +/- 0.13; respectively). These regional differences in prolyl endopeptidase enzyme content caused by one-kidney, one clip hypertension in neurosecretory and non-neurosecretory heart areas suggest that this enzyme plays a local role in the turnover of specific polypeptides.