To assess whether therapy with hydrochlorothiazide (HCTZ) or the calcium antagonist nitrendipine influences silent ischemia or arrhythmias, we studied 10 asymptomatic hypertensive male patients with positive Tl-201 scintigraphy in a double-blind, crossover protocol. Blood pressure (BP) and 48-h Holter monitoring were obtained after 2 weeks of placebo and 8 weeks each of HCTZ and nitrendipine therapy. Ischemia was defined as greater than 1 mm ST-segment depression lasting greater than 1 min and was quantified by the number of episodes, duration, and area under the curve (AUC). The mean number of PVCs per hour and the number of episodes of ventricular tachycardia (greater than 3 beats) were also assessed. Diastolic BP was significantly reduced by both HCTZ and nitrendipine (98 +/- 6 vs. 90 +/- 6 vs. 88 +/- 7 mm Hg, respectively, p less than 0.05), but systolic BP was unchanged for either drug. The number of ischemic episodes was reduced by nitrendipine, from 2.4 +/- 3 to 0.8 +/- 2, (p less than 0.05) but not by HCTZ (2.4 +/- 3 to 1.5 +/- 3, p = NS). The duration of ischemia (37 +/- 43 vs. 5 +/- 9 min, p less than 0.05) as well as the AUC (41 +/- 45 vs. 7 +/- 14 mm/min, p less than 0.05) were reduced only by nitrendipine. The number of PVCs rose with HCTZ therapy, from 19 +/- 34 to 69 +/- 88 (p less than 0.05) and was unchanged by nitrendipine (19 +/- 34 vs. 19 +/- 40, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)