To determine whether alteration of intrinsic myocardial stiffness is responsible for the reduction of left ventricular filling pressure and volume by nifedipine in patients with impaired baseline ventricular function, we evaluated the hemodynamic responses in 32 patients undergoing diagnostic cardiac catheterization. Micromanometric pressure and ventriculographic dimensional data were acquired before and 30 min after randomly assigned administration of nifedipine (20 mg sublingual) or placebo. A mathematical model requiring no assumptions about the stress-radius relationship or direct measurement of strain was used. No hemodynamic variables were changed after placebo. Left ventricular end-diastolic volume and pressure declined and cardiac output increased after nifedipine, particularly in subjects with impaired ventricular performance. Despite these salutary effects, intrinsic myocardial stiffness, elastic stiffness at a common level of stress, chamber stiffness, and rate of isovolumic relaxation were unchanged after nifedipine, even in patients with abnormal baseline ventricular function. The potent peripheral arteriodilator effect of nifedipine, rather than any direct myocardial or ventricular effects, appears to be responsible for the improved systolic and diastolic performance.