Fibrinolytic activity (FA) was measured by dilute blood clot lysis time at entry to the Northwick Park Heart Study in 1382 white men aged 40-64, of whom 179 subsequently experienced episodes of ischaemic heart disease during a mean follow-up period of 16.1 years. There was a significant interaction between age and low FA (p = 0.02) with respect to ischaemic heart disease: a difference of one standard deviation in FA was associated with a difference of about 40% in ischaemic heart disease risk (p = 0.002) in those aged 40-54 at entry. The FA association remained after adjusting for plasma fibrinogen. High fibrinogen concentrations themselves were also associated with ischaemic heart disease, as was high factor VII activity with fatal events. Low FA in younger men may exert a long-term influence by impairing the removal of fibrin deposits that contribute to atherogenesis. Low FA appears to be a leading determinant of ischaemic heart disease in younger men and methods of enhancing fibrinolytic activity, whether by life-style changes or pharmacologically, should be considered.