Variceal bleeding, whose triggering mechanisms are largely unknown, occurs with a circadian rhythmicity, with 2 peaks, one greater, in the evening, and one smaller, in the early morning. We assessed some clotting and hemodynamic parameters, possibly involved in variceal hemorrhage, over a 24-hour period, at 4-hour intervals, in 16 patients with cirrhosis and esophageal varices and in 9 controls. At each time interval, tissue plasminogen activator (tPA) and tPA inhibitor-1 (PAI-1) antigens and activities and total euglobulin fibrinolytic activity were determined and portal-vein flow velocity, volume, and congestion index were measured by duplex-Doppler. Significant circadian rhythms were searched for by least-squares and cosinor methods. tPA activity showed a circadian rhythm in cirrhosis, with a peak of 2.85 times the trough value, calculated at 18:42, and remained over 2.5-fold until shortly after 22:00. Total fibrinolytic activity showed a similar pattern, which was statistically significant also in controls. tPA and PAI antigens also showed significant circadian rhythm both in controls and cirrhotics, with higher values in the morning. Among the portal hemodynamic parameters only the congestion index showed significant rhythmic changes and only in cirrhosis, with the highest values in the late evening, but with limited diurnal excursion (ฯฎ 5.5%). In conclusion, we showed the existence of a circadian rhythm of fibrinolysis in cirrhosis, whose temporal distribution might suggest a role of fibrinolysis in variceal hemorrhage on the basis of the comparison to the known chronorisk of variceal bleeding. (HEPATOLOGY 2000;31:349-357.) Abbreviations: HCV, hepatitis C virus; PAI, plasminogen activator inhibitor; PT, prothrombin time; aPTT, activated partial thromboplastin time; t-PA act, tissue plasminogen activity; tPA Ag, tissue plasminogen activator antigen; u-PA act, urokinase plasminogen activator activity; u-PA Ag, urokinase plasminogen activator antigen; PAI act, plasminogen activator inhibitor activator; PAI Ag, plasminogen activator inhibitor antigen; MESOR, midline estimating statistic of rhythm; TEFA, total euglobulin fibrinolytic activity.