Cerebrovascular accidents are one of the life-threatening complications of diabetic ketoacidosis (DKA) in children and adolescents. Our objective was to evaluate the effect of DKA and its treatment on factors known to affect thrombotic activity (protein C; protein S; von Willebrand factor, fibrinogen; homocysteine; and folate) by comparing seven adolescents with DKA prior to treatment and at 6, 24, and 120 hours after initiation of treatment. We found that protein C activity was significantly decreased by DKA, but normalized slowly following treatment. Free protein S was low throughout the study. Protein C antigen and protein S antigen showed varying degrees ofchange within the first 24 hours, but remained in the normal range, with the exception of the initial value of protein C antigen, which was elevated. von Willebrand factor (vWF) antigen and vWF activity were both significantly increased prior to treatment, but decreased with treatment. However, vWF activity remained elevated at 120 hours. Fibrinogen concentrations showed no significant changes throughout the study. Homocysteine was significantly decreased prior to treatment and increased with the initiation of treatment Folate was significantly increased prior to treatment, and decreased to high normal levels. The increased vWF and the decreased levels of protein C activity and of free protein S support the hypothesis that DKA and its treatment results in a prothrombotic state and activation of the vascular endothelium, which, in turn, predispose to cerebrovascular accidents.