The aim of the present study was to document coagulation system activation and basal fibrinolysis in peripheral arterial occlusive disease (PAOD) at stage II of Fontaine's classification. In 34 patients, prothrombin fragment (F1 + 2), thrombin-antithrombin III complexes (TAT), and D-dimer concentrations were evaluated before and after a standard treadmill test. Basal levels in PAOD of F1 + 2 (1.25 +/- 0.19 nmol/liter) and of TAT (3.34 +/- 0.35 micrograms/liter) were significantly increased compared to those obtained in age- and sex-matched healthy controls (0.68 +/- 0.06 nmol/liter and 2.30 +/- 0.33 micrograms/liter, respectively), showing baseline activation of the clotting cascade. A secondary activation of the fibrinolytic system was evidenced by the highly significant increase of basal D-dimers (719 +/- 99 ng/dl in PAOD vs. 229 +/- 37 ng/dl in controls). Treadmill exercise failed to increase the study parameters significantly further. Walking distance (583 +/- 40 m) was correlated with the preexercise ankle to brachial systolic blood pressure ratio (r = 0.485, P < 0.005) and inversely with the level of D-dimers (r = -0.425, P < 0.02). Under baseline conditions, the latter parameter was correlated as well with the antigen concentration of urokinase-type plasminogen activator (u-PA; r = 0.503, P < 0.002). These results indicate that stage II PAOD is characterized by an activation of the clotting cascade in baseline conditions evidenced by increased F1 + 2 and TAT. A secondary activation of the fibrinolytic system with increased u-PA antigen levels accounts for the elevated D-dimers. Treadmill exercise was unable to increase these parameters further.