Several factors that modify the release of sarcoplasmic enzymes from skeletal muscle, with emphasis on data from isolated frog muscles, are reviewed. The evidence indicates that creatine kinase (CK) and lactate dehydrogenase (LDH) are released continuously from frog muscle fibers that have normal resting potentials and are presumably bound by an intact plasma membrane. The rates of release are determined not only by the transsarcolemmal efflux rates but also by the kinetics of the enzyme diffusion in the extracellular space. The release of CK and LDH is increased by sarcolemmal injury but is also stimulated by procedures that do not cause irreversible damage to membrane integrity as judged from morphological and electrophysiological parameters. Among these procedures are step changes in the tonicity of the bathing medium and brief exposure to nanomolar concentrations of polylysine or polyornithine, which increase the release rates from frog muscles by one order of magnitude. The possible mechanisms responsible for the efflux of sarcoplasmic enzymes and the relevance of these data to the increased enzyme loss from the muscles of patients with neuromuscular diseases are discussed.