In isolated human myocardium it was shown that a positive force-frequency relationship occurs in non-failing myocardium; however, the force-frequency relationship was found to be inverse in myocardium from failing human hearts. In order to investigate the clinical relevance of these experimental findings, the influence of heart rate changes on haemodynamics and left ventricular function was studied in eight patients without heart failure and in nine with failing dilated cardiomyopathy (NYHA II-III). Right ventricular pacing was performed at a rate slightly above sinus rate and at 100, 120 and 140 beats.min-1. Haemodynamic parameters were obtained by right heart catheterization and by high-fidelity left ventricular pressure measurements. Left ventricular angiography was performed at basal pacing rate and at 100 and 140 beats.min-1. With increasing heart rate, cardiac index increased in patients with normal left ventricular function from 2.9 +/- 0.2 to 3.5 +/- 0.21.min-1.m-2 (P < 0.01) and decreased continuously in patients with dilated cardiomyopathy from 2.6 +/- 0.1 to 2.2 +/- 0.1 l.min-1. m-2 (P < 0.05). With increasing heart rate, the maximum rate of left ventricular pressure rise increased in non-failing hearts from 1388 +/- 86 to 1671 +/- 88 mmHg.s-1 (P < 0.01) and did not change in failing hearts. Ejection fraction decreased from 27 +/- 3% to 19 +/- 2% in patients with dilated cardiomyopathy (P < 0.05) when the pacing rate was changed from 84 +/- 2 beats.min-1 to 140 beats.min-1, which was associated with a significant increase in end-systolic volume without significant changes in end-diastolic volume.(ABSTRACT TRUNCATED AT 250 WORDS)