Raised plasma PAI-1 and t-PA antigen levels are known risk factors for acute coronary events. It is not known whether these factors are related to coronary thrombosis or to a possible atherosclerotic background. Both factors show a marked circadian variation in blood. To assess the effect of atherosclerosis on the fibrinolytic balance, we measured plasma t-PA and PAI-1 antigen levels 3-hourly for 24 hours in 7 patients with severe atherosclerosis (AS group) and in 10 healthy controls (C). Age of AS and C did not differ significantly. In both AS and C, t-PA and PAI-1 levels were highest between 3:00 h and 9:00 h, and lowest between 18:00 h and 24:00 h. The 24 h-averaged level of t-PA (median and interquartiles) was significantly higher in AS than in C [13.8 (10.5-16.0) vs. 7.3 (4.7-7.9) μg/L, p = 0.002]. The 24 h-averaged level of PAI-1 also tended to be higher in AS vs. C, but the difference did not reach statistical significance [17.9 (17.3-20.8) vs. 13.7 (10.3-18.6) μg/L, p = 0.09]. In C, but not in AS, t-PA levels correlated significantly with those of PAI-1 (r = 0.37, p = 0.0001 in C vs. r = 0.05, p = 0.9 in AS). Thus, patients with severe AS, compared with C, have significantly higher plasma concentrations of t-PA antigen throughout the 24 hours, which are not correlated to PAI-1. The association between raised t-PA antigen and coronary events may be mediated by underlying atherosclerosis.