A double-blind, randomized, placebo-controlled, crossover study tested peak and trough efficacy of immediate-release nisoldipine (20 mg twice daily) added to existent beta-adrenergic blocking therapy. Patients were randomized with a history of chronic stable angina, while receiving a stable regimen of a beta-blocking agent, with exercise test-induced angina in association with 1 mm horizontal or downsloping ST-segment depression and exercise test reproducibility of +/- 15%. Ambulatory electrocardiographic monitoring (48-hour) was performed at 3 of 5 centers (44 patients). Efficacy was achieved in 53 patients (26 taking immediate-release nisoldipine/placebo in sequence and 27 taking placebo/immediate-release nisoldipine in sequence). Total exercise time increased compared with placebo at peak, but only a trend was seen at trough. Time to 1 mm ST-segment depression at peak and trough and ambulatory electrocardiographic parameters were also improved. Adverse effects were mild. This trial confirms that immediate-release nisoldipine when added to existent beta-blocker therapy is an active antianginal and anti-ischemic agent, but that the immediate-release formulation loses its antianginal effect at the end of its dosing interval (9 to 14 hours). This drug is therefore being examined in a new extended-release formulation (Coat-Core).