Remote-zone left ventricular dysfunction (LVD) contributes to global reductions in contractile function after localized myocardial infarction (MI). However, the underlying molecular mechanisms underlying this form of LVD are not clear. This study tested the hypothesis that myofibrillar protein function is directly affected in remote-zone left ventricular dysfunction early after MI. Cardiac myosin and native thin filaments were purified from mouse myocardium taken from both the non-necrotic zone adjacent to, and the non-ischemic zone remote from an infarct induced by 1 hr of coronary occlusion followed by 24 hr of reperfusion. Thin filament velocities were measured using the in vitro motility assay. Results showed that overall function was significantly reduced in samples from both the adjacent (43 ± 12% of control, n=7) and remote (53 ± 8% of control, n=13) zones when compared to control proteins (p < 0.05). Myosin from the remote-zone propelled control thin filaments at reduced velocities similar to those measured above. In contrast, the calcium sensitivity of remote-zone thin filaments over control myosin was unchanged from control thin filaments (half-maximal at pCa 6.32±0.08 and 6.27±0.06, respectively) but showed a 20% increase in velocity at saturating calcium that parallels an increase in tropomyosin phosphorylation. Myosin dysfunction may be related to oxidation of cysteines in the myosin heavy chains or carbonylation of myosin binding protein-C. We hypothesize that phosphorylation of tropomyosin may serve a compensatory role, augmenting contraction during periods of oxidative stress when myosin function is compromised.