The effect of cold-restraint stress on platelet function in vitro was studied in the rat model. Platelet function was assessed by platelet aggregation in response to adenosine diphosphate (ADP) and thrombin. ADP-induced platelet aggregation was reduced in platelet-rich plasma after 2 h of cold-restraint stress. Thrombin-induced platelet aggregation was reduced with time during cold-restraint stress with a parallel increase in the lesion index. Although pretreatment of animals with atropine prevented the development of gastric mucosal lesions, platelet dysfunction was not reversed by this treatment. These results suggest that cold-restraint stress may impair platelet function, probably due to platelet activation in vivo, and that the abnormalities in platelet function may be associated with the development of gastric mucosal lesions.