The fibrate group of drugs are widely used to lower plasma lipid concentrations, especially in diabetic subjects. They exert their effects by activating peroxisome proliferator-activated receptor α (PPARα), which regulates the transcription of a number of genes involved in hepatic lipid metabolism. The discovery of polymorphisms in the PPARα gene raises the possibility that different variants could be associated with different responses to fibrate therapy. We have examined this in a random sample of 96 lipid clinic subjects who showed a wide range of response to fibrates. Of the known polymorphisms in PPARα, the only difference detected in this sample was the Leu/Val change at position 162. However, this change did not influence baseline plasma cholesterol or triacylglycerol concentrations, and was not associated with any difference in the effectiveness of fibrate treatment. Thus, there is no evidence that variation in the PPARα gene at position 162 is responsible for the differential response to fibrates in non-diabetic hyperlipidaemic subjects.