SummaryCoronary artery disease is frequently associated with disturbed blood lipids and with a deficient blood fibrinolytic capacity. In order to investigate a possible link between hypercholesterolemia and hypofibrino-lysis, we have investigated the effect of simvastatin, a HMG-CoA reductase inhibitor, on blood lipids and fibrinolytic parameters in a double blind, randomized, placebo controlled study design. Twenty-four male patients, aged between 42 and 65 years, with angiographically confirmed coronary artery disease, were selected from a series of 731 consecutive patients on the basis of a fasting serum cholesterol level of more than 250 mg/dl and a plasma PAI-I level of more than 60 ng/ml. Patients were randomly assigned to 20 mg of simvastatin daily (Group I), or placebo (Group II), for four weeks, followed by doubling of the dose for another four weeks. Blood samples were obtained at baseline and at 4 and 8 weeks. Groups I and II did not differsignificantly at baseline. As expected, simvastatin produced a significant reduction in serum levels of total cholesterol (33±12 and 36±12 percent, mean±SD, after 4 and 8 weeks respectively, p<0.001 vs baseline), LDL-cholesterol (36±5 and 43±6 percent respectively, p<0.00 I vs base line) and a polipoprote in-8 (20±29 and 23±30 percent respectively, p<0.05 vs) baseline), whereas these parameters did not change significantly in the place bo group. The PAI-I levels decreased to a compara bleex tent in both groups (54±34 and 51±3 1 percent after 4 and 8 weeks repectively in the sim vas tatin group and 58±29 and 37±38 percent in the place to group p<0.0 I vs baseline), whereas t-PA decreased be tween 15 and 20 percent in both groups. These findings suggest the at there is no causal relationship between hypercholesterolemi a and its associated changes in blood lipids on the one hand , and) decreased blood fibrinolytic capacity on the other hand. The comp arable decreases of PAI-I levels in both groups are probably secundary to improved dietary control during the study peri od. although no significant changes in plasma insulin level or body weight were observed.