AIMS: To assess whether response to cardiac resynchronization therapy (CRT) is related to myocardial viability in the paced left ventricular (LV) region, evaluated by contractile reserve (CR). Non-response to CRT may partly be due to inefficient pacing by the LV lead located in a fibrotic area. METHODS AND RESULTS: Nineteen patients (64 +/- 13 years, 14 men, 9 ischaemic) with severe heart failure (EF = 27 +/- 8%, QRS = 154 +/- 25 ms) were included in the week after device implantation. Stroke volume (SV) and LV dyssynchrony (by Tissue Doppler Imaging) were successively assessed with CRT on and CRT off. Afterwards, CRT device was maintained off during dobutamine infusion to assess CR in the LV-pacing region. LV end-systolic volume (ESV) was assessed after 6 months to quantify reverse remodelling. CR in the paced LV region (n = 10, 5/9 ischaemic and 5/10 non-ischaemic) was correlated to a reduction in LV dyssynchrony under CRT (120 +/- 76 vs. 78 +/- 64 ms, P = 0.02). Conversely, LV dyssynchrony was unchanged (161 +/- 100 vs. 163 +/- 80 ms) without CR. In desynchronized patients (>65 ms, n = 15), increase in SV under CRT and changes in ESV at 6 months were +22 and -18%, respectively, when CR was present and 0% and +9%, respectively, when absent. CONCLUSION: Acute haemodynamic response and reverse remodelling under CRT require viability in the target region of LV lead.