The effects of long-term treatment with diltiazem on the heart in normotensive (WKY) and spontaneously hypertensive rats (SHR) were studied. Diltiazem was added to the drinking fluid (900 mg/liter) and given ad libitum from 19 to 26 weeks of age, whereas tap water was given to the control animals. Although diltiazem did not decrease blood pressure in SHR, it decelerated the increase in their left ventricular weight (p less than 0.01). Hearts were removed and perfused by the working heart technique for 15 min, and then global ischemia was induced for either 10 or 30 min. The ischemic heart was reperfused for 30 min. The extent of recovery of coronary flow after reperfusion, following 30 min of ischemia in the diltiazem-treated SHR, was higher than that in the control SHR (p less than 0.01). The levels of adenosine triphosphate (ATP), creatine phosphate (CrP), and energy charge potential in the SHR heart reperfused after 30 min of ischemia were lower than those in the reperfused WKY heart (p less than 0.01, respectively). Diltiazem improved the restoration of ATP and CrP and prevented the decrease in energy charge potential in SHR after reperfusion following 30 min of ischemia (p less than 0.01, respectively). In conclusion, long-term treatment of SHR with diltiazem may protect the myocardium when myocardial ischemia occurs.