Recent studies indicate that the incidence of thromboembolic events is increasing as a secondary complication in children with serious underlying diseases. The mechanism to eliminate these thrombi via the thrombolytic system in children is unknown. The baseline fibrinolytic system is age dependent, with significant variation between children and adults. Adult studies would suggest that the fibrinolytic response to venous occlusion has more clinical relevance than the baseline fibrinolytic system. The aim of this study was to determine whether the fibrinolytic response to venous occlusion stress testing in healthy adolescents differs from the response in healthy adults. Healthy adolescents (13-18 y) from a school population and normal adults were recruited. Pre- and postvenous occlusion blood samples were collected using standard techniques. Plasma tissue plasminogen activator, plasminogen activator inhibitor-1, plasminogen, alpha(2)-antiplasmin, alpha(2)-macroglubulin, D-dimers, euglobulin lysis time, and fibrinogen were measured on each sample. Adolescents had significantly decreased tissue plasminogen activator antigen levels and increased plasminogen activator inhibitor-1 activity levels after venous occlusion, resulting in significantly prolonged euglobulin lysis times. The results of our study confirm developmental differences in the fibrinolytic response to venous occlusion stress testing. The age-related differences in fibrinolytic response to venous occlusion of younger children and the significance of these differences on the pathophysiology of thromboembolic events in children require further studies.