Due to the invasive nature of myocardial biopsies, a complication rate of up to 2.5%, and the limitations, e.g., at focal distribution of rejection, there is a continuous need for reliable, non-invasive parameters in recognizing moderate (grade 2) and severe (grade 3) acute cardiac allograft rejections in patients treated with cyclosporine A. 64 biopsies of 20 patients with previous heart transplantations in the past 3 weeks to 36 months (mean 11 months) were compared prospectively to Doppler and echocardiographic results. Parameters of systolic function such as percent fractional shortening (FS) and systolic wall thickness of the posterior wall (SWT) remained without significant changes at grade 2 and grade 3 rejections. The same is valid for relaxation parameters such as maximum velocity of posterior wall reduction (PTR), the time interval of endsystole to maximum velocity of posterior wall reduction (tES-PTR), and the isovolumic relaxation time (IVRT). Left-ventricular filling parameters such as maximum early diastolic flow velocity (VEmax) increased significantly from 73.3 +/- 15.2 cm/s in the rejection-free interval (grade 0) to 103.9 +/- 15.0 cm/s at grade 2 rejection and 101.1 +/- 9.2 cm/s at grade 3 rejection (both p < 0.001). A sensitivity of 50% and a negative predictive value of 77% are, however, too low to diagnose or exclude a moderate or severe acute rejection in the individual case.(ABSTRACT TRUNCATED AT 250 WORDS)