Conventional activation mapping in the dilated human left ventricle (LV) with left bundle-branch block (LBBB) morphology is incomplete given the limited number of recording sites that may be collected in a reasonable time and given the lack of precision in marking specific anatomic locations. We studied LV activation sequences in 24 patients with heart failure and LBBB QRS morphology with simultaneous application of 3D contact and noncontact mapping during intrinsic rhythm and asynchronous pacing. Approximately one third of the patients with typical LBBB QRS morphology had normal transseptal activation time and a slightly prolonged or near-normal LV endocardial activation time. A "U-shaped" activation wave front was present in 23 patients because of a line of block that was located anteriorly (n=12), laterally (n=8), and inferiorly (n=3). Patients with a lateral line of block had significantly shorter QRS (P<0.003) and transseptal durations (P<0.001) and a longer distance from the LV breakthrough site to line of block (P<0.03). Functional behavior of the line of block was demonstrated by a change in its location during asynchronous ventricular pacing at different sites and cycle lengths. A U-shaped conduction pattern is imposed on the LV activation sequence by a transmural functional line of block located between the LV septum and the lateral wall with a prolonged activation time. Assessment of functional block is facilitated by noncontact mapping, which may be useful for identifying and targeting specific locations that are optimal for successful cardiac resynchronization therapy.