The use of lisinopril was assessed in inducing regression of established left ventricular hypertrophy. Left ventricular hypertrophy was achieved by aortic constriction in the rat. Lisinopril was administered in drinking water (5 mg/kg body weight/day) to aortic constricted rats starting from Day 30 for a period of further 30 days. At the end of 60 days the rates of protein synthesis were measured using the flooding dose technique. Lisinopril reduced the mixed protein contents of the regressed left ventricle from 223 +/- 7 mg to 175 +/- 10 mg/left ventricle in the aortic constricted rats; P < 0.01, all data are means +/- SEM, n = 5-8. The regression of left ventricular mass occurred along with simultaneous decrease in the rate of protein synthesis (i.e., 6.56 +/- 0.33 in aortic constricted rats versus 4.40 +/- 0.44%/day, in lisinopril treated left ventricles, P < 0.05). However, the expanded cardiocyte fiber thickness remained unchanged despite lisinopril treatment (i.e., 20.4 +/- 0.7 in aortic constricted rats versus 19.5 +/- 0.6 microm in regressed left ventricles, P > 0.05). The results indicate that regression of pressure overloaded hypertrophy with lisinopril primarily occurs by a decrease in protein synthesis in the connective tissue components of the left ventricle, although cytoskeletal components may be unaffected.