The effects of three commonly used antihypertensive agents (captopril, hydralazine, and terazosin) on tissue antioxidant enzymes and lipid peroxidation in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY rats) were studied by analysis of antioxidant enzyme specific activities and lipid peroxidation levels in control and drug-treated animals. In the myocardium, changes in some of the enzyme activities between normotensive WKY and hypertensive SHR rats were mitigated by treatment of the SHR rats with an antihypertensive drug. Thus, all three drugs caused significant increases in myocardial Cu/Zn superoxide dismutase (up to 133% of SHR control activity) and decreases in glutathione peroxidase (down to 59% of SHR control activity) to values that were closer to those in untreated WKY rats. Captopril also increased Mn superoxide dismutase activity, and hydralazine and terazosin decreased catalase activity towards untreated WKY values. Hydralazine was the only drug to alter the lipid peroxidation level in the myocardium of SHR rats (a 28% decrease), but in WKY rats all three drugs caused significant decreases in myocardial lipid peroxidation levels. In WKY rats, none of the drugs affected myocardial Mn and Cu/Zn superoxide dismutase activities, although glutathione peroxidase activity was decreased by hydralazine and terazosin treatment and catalase activity was increased by captopril treatment. Enzyme activity changes in liver and skeletal muscle indicated that such changes were often tissue specific. No pattern was found for coordinated changes in antioxidant enzyme expression as a result of the drug treatments, and the changes in antioxidant enzyme specific activities did not correlate generally with changes in lipid peroxidation levels.