The contraction of striated muscle is due to cyclical, ATP-driven interactions of the motor protein myosin II with actin. In each sarcomere, the ~2 μm long structural unit of striated muscle, two bipolar arrays of myosin motors emerging from the thick filament overlap with the thin, actin containing, filaments originating from the ends of the sarcomere. A structural working stroke in the myosin head, accompanied by the release of the ATP hydrolysis products (g-phosphate (Pi) and ADP), generates force and relative filament sliding pulling the actin filament towards the centre of the sarcomere. In each half-sarcomere, the myosin motors are mechanically coupled as parallel force generators via their attachment to the thick filament, and the collective motor formed by the array of myosin motors, the interdigitating actin filaments and other cytoskeleton and regulatory proteins is the basic functional unit of muscle. When the external load is smaller than the isometric force generated by the motor array, the actin filament slides past the myosin filament and the sarcomere shortens at a velocity that is larger at lower loads (force-velocity relation), accompanied by the increase in the rates of ATP-driven detachment-attachment cycles and energy liberation. Power output is maximum when muscle shortens under a load ~1/3 the isometric force, at which the ATP is split~ four times faster than in isometric contraction and macroscopic efficiency is 40% (1). In vitro X-ray crystallography and cryo-EM studies have provided a high resolution description of the structure of the actomyosin complex, leading to a model of the working stroke that consists in a 70° tilting of the light chain domain of the myosin that links the actin-attached catalytic domain to the tail and the myosin filament (2). In situ such a model accounts for the 11-nm filament sliding following a sudden drop of the load to zero (3). However, both in situ and in vitro evidences that the motor compliance is relatively low (0.35 nm/pN) suggest that, based on energetic considerations, the working stroke must be a multi-step structural transition with only the first few steps responsible for the generation of the isometric force. One relevant, still unsolved question emerges about the coupling between structural and mechanical events accompanying the release of the ATP hydrolysis products under different loads. The question whether the working stroke is associated with Pi release has been addressed by in situ measurements of the working stroke and its kinetics under the loads the myosin motor experiences as a part of a collective motor. In those experiments, fast-sarcomere-level mechanics on demembranated fibres from rabbit psoas was used to determine how the Pi concentration ([Pi]) modulates the number and force of actin-attached myosin motors during isometric and isotonic contractions. In isometric conditions the increase in [Pi] reduces the isometric force because of a proportional reduction in the number of attached myosin motors without reduction of the force per motor (4). The Pi-dependent reduction in isometric force is not accompanied by a proportional reduction in the rate of ATP hydrolysis (5), suggesting that under high load a motor that has already undergone the force generating transition can detach at an early stage of the ATPase cycle, then rapidly release the hydrolysis products and bind another ATP. In isotonic conditions the velocity transient following a force step has an early rapid shortening component, which represents the mechanical manifestation of the working stroke. By determining the effect of [Pi] on the velocity transient it was found that the working stroke is not affected by the increase in [Pi], while the subsequent transition to the steady shortening velocity is accelerated and the steady power at high loads is reduced (6). A chemo-mechanical model in which the working stroke and Pi release are orthogonal processes has been demonstrated to be able to reproduce the load dependence of velocity transient, as well as steady shortening and power. In the model biochemical and mechanical steps are not tightly coupled: (i) the release of the hydrolysis products from the catalytic site of a myosin motor can occur at any stage of the working stroke, though progression in the working stroke increases the rate constants of product release, and (ii) a myosin motor, in an intermediate state of the working stroke, can slip to the next actin monomer away from the center of the sarcomere before terminating the biochemical cycle. The model provides the molecular explanation of the relation between the rate of energy liberation and shortening velocity during muscle contraction (7). Supported by MIUR-PRIN and Telethon (Italy).