Platelets play a central role in hemostasis during vascular injury. Patients affected with the hemorrhagic syndrome caused by contact with Lonomia achelous caterpillars (Lac) Lepi- doptera distributed in various South American countries, show digestive, pulmonary and intraperitoneal bleeding in combination with hematomas and echymosis. In the present study, we have evaluated the effects of Lonomin V (serine protease isolated from Lac hemolymph) on some functional properties of platelets, evaluating its importance in primary hemostasis. Platelet adhesion to fibrinogen was reduced by 19, 20, 36, and 37% after pre-treated with 0.2, 2, 20 and 40 nM of Lonomin V, respectively. Pre-incubation of the platelets with 408 nM of Lonomin V, for 4 min at 37 C, resulted in complete inhibition of the collagen-induced platelet aggregation, in contrast to 56% inhibition of the ADP - induced platelet aggregation. Lonomin V also inhibited anti-aIIbb3 integrin binding to platelets by 56, 57, 52 and 54% at concentrations of 0.2, 2, 20 and 40 nM respectively. Additionally, Lonomin V inhibited anti-P-selectin binding to platelets by 28, 37, 33 and 33% at the same concentrations. The platelets tested with Lonomin V did not modify their viability. In summary, Lonomin V inhibited platelet aggregation, probably caused by the degradation of collagen. The anti-platelet activity of Lonomin V has been shown to be unique and a potentially useful tool for investigating cell-matrix and cell–cell interactions and for the development of antithrombotic agents in terms of their anti-adhesive activities.This work was funded by a grant from the Science and Technology Fund (FONACIT) programs (PG-2005000400), and by the Venezuelan Institute of Scientific Research (IVIC), Caracas, Venezuela.