The fatty acid composition of phospholipids from differentiated human neuroblastoma SH-SY5Y cells, human and rat brain tissue and rat brain synaptosomes was determined using high pressure liquid chromatography. Comparison of the fatty acid composition of the cells with that derived from brain tissue identified differences in the cells including a profound deficit of docosahexaenoic acid and an elevation of arachidonic acid. The phospholipid fatty acid content could be modified by addition of free fatty acids to the growth medium, and this was shown to influence the susceptibility of the SH-SY5Y cells to the cell death induced by a mitochondrial toxin, 3-nitropropionic acid.