In this review we have attempted a synthesis of ideas from cross-bridge theories of muscle contraction with biochemical mechanisms of the actomyosin ATPase. This synthesis of ideas has been based on experimental approaches that permit mechanical and biochemical investigations on the same system. We have formulated an example of how biochemical processes may be influenced by strain in the cross-bridge and have highlighted how much has yet to be learned about the biochemistry (and protein structure) of the working stroke of the cross-bridge. Processes that do not appear to be related to the working stroke such as ATP-induced dissociation of actomyosin or protein-bound ATP hydrolysis appear to be similar kinetically in fibers and isolated actomyosin. But, as might be expected, this is not the case in those processes that involve force production and the performance of mechanical work. There appears to be a sound base from which the mechanochemistry of individual processes within the cross-bridge cycle can be analyzed in detail. There is a need for the development of spectroscopic techniques, particularly those that might detect the rate of Pi and ADP dissociation from cross-bridges into the medium. The combination of pulse photolysis of caged ATP and time-resolved structure analysis by use of synchrotron radiation (53) should lead to better understanding of the structure of cross-bridge states in relation to the chemistry and mechanics of transient intermediates.