In a study of 20 patients with hypercholesterolemia (type IIa) the effects of lovastatin (20-80 mg/day) on various clotting and thrombosis parameters were monitored for 12 months. On 11 occasions various cholesterol fractions and clotting parameters were determined in each patient. In addition, the clotting inhibitors AT III, protein C, protein S, and C1-esterase inhibitor and the fibrinolysis parameters plasminogen and alpha 2-antiplasmin were examined. Platelet function was monitored on the basis of spontaneous and induced (collagen, ADP, epinephrine, ristocetin) aggregation. Lovastatin in the above dosage brought about a 66 mg/dl (from 320 +/- 12.6 to 254 +/- 12.0 mg/dl) reduction in the total cholesterol level and a 56 mg/dl (from 244 +/- 11.4 to 188 +/- 12.1 mg/dl) reduction in LDL cholesterol at the end of the study. Fibrinogen showed a significance decrease during the study period, whereas PT and aPTT remained unaffected. The initial slopes of the ADP-induced platelet aggregation revealed a significant decrease. C-reactive protein and platelet count remained within the normal range, indicating no significant change. Thrombin clotting time, AT III, C1-esterase inhibitor, plasminogen, and alpha 2-antiplasmin were not modified. Protein C and S behaved in a contradictory way, but remained within the normal range. Long-term treatment with lovastatin was associated with a significant reduction of fibrinogen levels and platelet aggregation induced by ADP in type-IIa hypercholesterolemic patients. These alterations, as well as their role in cardiovascular disease, should be the subject of further investigations.