Damage to skeletal muscles may be mediated via free radicals or intracellular calcium overload. To look for inter-relationships between these pathways we have examined the effect of intracellular Ca overload on muscles from rats fed on either a vitamin E-deficient or vitamin E-sufficient diet and assessed the non-enzymic lipid peroxidation in these muscles by examining the production of thiobarbituric acid reactive substances by homogenates. Vitamin E-deficient muscles were more susceptible to Ca-induced intracellular enzyme efflux and this was acutely corrected by supplementation of the external medium with 230 mumol alpha-tocopherol/l. Vitamin E-deficient muscles showed increased levels of basal lipid peroxides and were more susceptible to iron-catalysed lipid peroxidation. Addition of the Ca ionophore A23187 increased lipid peroxidation in vitamin E-deficient muscle homogenates, but had the opposite effect in vitamin E-sufficient muscles. These results demonstrate that vitamin E-deficient muscle has an increased susceptibility to intracellular Ca overload, but that this effect cannot be explained by a direct stimulatory effect of the ionophore on non-enzymic lipid peroxidation.