The underlying events during rapid cellular damage have been studied in a variety of cells, particularly kidney, hepatocytes and muscle cells, although the initial lesions are very different, being genetic (e.g. Duchenne muscular dystrophy, see Jackson, McArdle & Edwards, this volume; or malignant hyperthermia, see Arthur & Duthie, this volume), or the response to toxic agents, or the result of endocrine dysfunction or a failure in metabolism. It has been suggested that there may be final common pathways, or that there may be a common central trigger. In particular, Ca2+ has been proposed as having a major role in initiating and regulating these events in cell death and toxic cell killing (Duncan, 1978; Schanne et al., 1979; Farber, 1981; Trump, Berezesky & Osornio- Vargas, 1981; Nayler, 1983; Orrenius et al., 1989) and consequently these studies have concentrated on the ways in which the initial lesion may result in changes in the intracellular concentration of free Ca2+ ([Ca2+]i) and on the pathways that may be activated by a rise in [Ca2+]i. For example, the missing gene product (dystrophin) in Duchenne muscular dystrophy and in mdx mice has been identified as a sub-sarcolemma cytoskeletal protein and it remains to be explained how its absence leads to the rise in [Ca2+]i that has been measured, and to the breakdown of the sarcolemma myofilament apparatus (see Duncan, 1989a). There is little doubt that a rise in [Ca2+]i can precipitate rapid cell damage; it can be produced experimentally by exposure of cells to the divalent cation ionophore A23187 and an elevated [Ca2+]i has been measured in such conditions as malignant hyperthermia (Lopez et al., 1985).