In a previous pilot study that did not reach statistical significance, intermittent single-leg pneumatic compression appeared effective in reducing the incidence of calf vein thrombosis not only in the pumped calf but also in the unpumped leg in 37 patients, using the 125I-fibrinogen (Abbott Laboratories) technique. The present study was undertaken to investigate mechanical induction of local and systemic fibrinolysis. The euglobulin lysis time in the arm venous effluent was determined in five volunteers before and after unilateral arm compression for 1/2 hour. Shortening averaged 19% (not significant). The experiment was repeated using bilateral calf-length boots with femoral vein sampling. Euglobulin lysis decreased 22% (P < 0.001). To uncover possible systemic effects, the protocol was altered using calf boots with sampling from the arm. The euglobulin lysis diminished 6% in 57 volunteers (P < 0.001). In 27 others the effects of thigh-length and calf-length boots were compared. In half, pumping with a short boot was undertaken first, and in the remainder, the long boot was applied initially. One-half hour of pumping was followed by 1/2 hour of rest. Immediately afterward the second period of pumping took place and continued for 1/2 hour. A total of four arm vein samples were obtained, one before and after each pumping period. Although, in retrospect, the 1/2-hour rest period was inadequate to permit the subjects to return to basal conditions, statistically significant decreases in euglobin lysis time (P = 0.05) occurred with the long boots. This study shows intermittent calf compression increases fibrinolytic potential locally and this effect can be demonstrated systemically. The greater the volume of tissue compressed, the greater the response. The efficacy of intermittent venous compression in reducing the incidence of deep venous thrombosis may be due, in part, to localized induction of fibrinolysis.