It has been suggested that accumulation of lipid metabolites, such as fatty acids, fatty acyl-CoA and acylcarnitine, in the ischaemic myocardium, may be responsible for disturbances in mitochondrial Ca2+ fluxes. In view of the presence of an intracellular fatty acid binding protein, the question arose whether these intermediates affect mitochondrial Ca2+ uptake and release similarly in vivo. In this study the effects of linoleic acid, palmitic acid, palmitoyl-CoA and palmitoylcarnitine were studied on mitochondrial Ca2+ fluxes in the absence and presence of albumin, an avid binder of fatty acid derivatives. Albumin reversed the effects of the above compounds on mitochondrial Ca2+ uptake and release, suggesting that the presence of an intracellular fatty acid binding protein may protect the ischaemic myocardial cell against the deleterious effects of accumulated fatty acid derivatives.