There is a non-linear discontinuous relationship between serum cholesterol, and LDL cholesterol, with IHD. There is no sound evidence that reduction of serum cholesterol below 200-210 mg/dl will reduce IHD incidence. It has not yet been shown that regression of advanced lesions in middle-aged men can occur, but regression of cholesterol-induced atheromatous lesions has been achieved in juvenile monkeys by discontinuing atherogenic diets. While the three major primary prevention trials of lowering raised serum cholesterol were all associated with reduction in the non-fatal mortality from IHD--thereby supporting the lipid hypothesis--all also showed an increase in non-cardiovascular mortality. It is legitimate to raise doubts about the consequences on normal biological function of ageing cells of reducing cholesterol concentrations over many years. It is probably of little value to reduce raised serum cholesterol concentrations in patients with overt IHD, since their prognosis is largely determined by the extent of myocardial damage sustained and of coexisting thrombogenic tendency. Patients with familial hypercholesterolaemia should be vigorously treated with a diet with a P/S ratio 1-5, cholestyramine and perhaps nicotinic acid also. The general population should be advised to reduce fat calories to below 30 per cent of total energy with no more than one-third from saturated fat.