Hearts of 11 anesthetized open-chest dogs were paced from the right atrium (RA), right ventricular outflow tract (RVOT), and left ventricular apex (LVA). Maps of the sequence of electrical activation (192 electrodes), fiber strain (video technique), and blood flow (microsphere technique) in the epicardial layers were obtained from a 15- to 20-cm2 area of the anterior left ventricular wall. Electrical asynchrony in this area was 10 +/- 5 (RA), 52 +/- 12 (RVOT), and 30 +/- 16 ms (LVA, mean +/- SD, P less than 0.05 for RVOT and LVA compared with RA). Epicardial fiber strain during the ejection phase was uniformly distributed during RA pacing. However, during ventricular pacing it ranged from 13 +/- 33% (RVOT) and 23 +/- 29% (LVA) of the value during RA pacing in early-activated regions to 268 +/- 127% (RVOT) and 250 +/- 130% (LVA) of this value in late-activated regions. Epicardial blood flow ranged from 81 +/- 22% (RVOT) and 79 +/- 23% (LVA) in early-activated regions to 142 +/- 42% (RVOT) and 126 +/- 22% (LVA) in late activated regions. In all above values P less than 0.05 compared with RA. During RVOT pacing, gradients of epicardial electrical activation time, fiber strain, and blood flow pointed in the same direction. Compared with RVOT pacing, during LVA pacing all gradients were opposite in direction, and the gradients of electrical activation time and blood flow appeared to be smaller. These results indicate that timing of electrical activation is an important determinant for the distribution of fiber strain and blood flow in the left ventricular wall.