A method to induce microthrombi in small mesenteric arteries (phi 15-25 microns) has been developed to study platelet reactions and to investigate antithrombotic drugs. A high power water immersion interference contrast system, based on a Leitz Orthoplan microscope, was used. In Nembutal-anesthetized male Wistar rats and in fawn hooded bleeder rats, vascular lesions were produced with a Hadron-512-Ruby-bio-laser or with a Coherent CR-2 supergraphite ion laser (Argon laser). The ruby laser produced intravascular precipitates consisting of proteins and erythrocytes which usually stuck to the vessel wall and on which platelets immediately adhered, transformed with pseudopode formation and formed loose aggregates. The Argon laser induced vascular damage, usually without intravascular heat precipitates which also led to platelet adhesion, transformation and aggregation. Fibrin threads rarely formed in the early platelet thrombi. Thrombus formation was significantly reduced in this model by dipyridamole (10 mg/kg orally), by Ditazole (50 mg/kg orally), heparin (100 IU/kg i.v.), Molsidomine (50 mg/kg orally), Nafazatrom (Bay G 6575, 10 mg/kg i.v. and orally), Ticlopidine (100 and 200 mg/kg orally) and Tioxaprofen (EMD 26644, 10 mg/kg orally). Thrombus formation was also significantly reduced in fawn hooded bleeder rats.