Radionuclide-derived left ventricular ejection fraction (LVEF) is used to assess LV systolic function, to follow trends in the natural history of dilated cardiomyopathy, and to prioritize patients waiting for cardiac transplantation. Reproducibility of LVEF at extremely low levels has not, however, been reported. To assess the reproducibility of radionuclide LVEF at levels below 0.30 EF U, 17 highly symptomatic patients (NYHA Class III/IV) with dilated cardiomyopathy were studied on two occasions, 72 hours apart. Sequential scans were analyzed by two independent observers. Mean LVEF was 0.18±0.06 U (scan 1) and 0.17±0.06 U (scan 2). Interoperator reproducibility (SD) was 0.03 U (R=0.76), interscan reproducibility (SD) was 0.03 U (R=0.62), and overall reproducibility (SD) was 0.04 U (R=0.50). The interobserver variation of 0.03 (actually 0.027) was just over one half that seen in normal volunteers (variation 0.05, n=29) studied previously in this department. A change of ≥0.08 U (2SD) in either direction is highly likely to represent a real change in LV function in those with LVEF ≤ 0.30 units, compared with the change of at least 0.10 units required in those with normal LV function. Lower interobserver and interscan reproducibility should be taken into account when interpreting sequential scans in patients with severe LV dysfunction.