A study was made of the acute effects of orally administered nethalide on the subjective and electrocardiographic responses to treadmill exercise in 11 patients with angina pectoris. Nethalide lowered the standing heart rate at rest and the maximum heart rate attained with exercise whether or not nitroglycerin was used concurrently. No consistent change in exercise capacity or time of onset of anginal pain and electrocardiographic abnormalities was noted after nethalide administration in the doses used in this study. However, the combination of nethalide and nitroglycerin in most subjects caused a strikingly greater exercise tolerance and delay in the onset of pain and electrocardiographic changes than did nitroglycerin alone.