Patients with end-stage renal disease use hemodialysis catheters for either temporary or permanent blood access. Recurrent thrombosis and fibrin sheath formation are common causes of poor or inadequate blood flow rates that require intervention. We studied the effect of tissue plasminogen activator (tPA) in reestablishing adequate blood flow rates through nonfunctional vascular catheters in 22 consecutive chronic hemodialysis patients. From January 1, 1999, to May 20, 1999, there were 56 instances in which tPA was used in an attempt to improve blood flow rates. In all instances, 2 mg of tPA was infused into each port of a dual-lumen internal jugular catheter. Dwell time ranged between 2 and 96 hours (median, 24 hours), and patient follow-up ranged between 47 and 140 days (median, 133.5 days). tPA was effective in establishing adequate blood flow rates (>/=200 mL/min) during the next dialysis session in 49 of 56 cases (87.5%). Seven additional interventions were required because of early or late tPA failure (one fibrin sheath stripping, one catheter replacement for kinking, one catheter replacement for central venous stenosis, and four catheter replacements for persistently poor blood flow rates), and eight catheters were replaced for infection. Thus, further interventions to achieve adequate blood flow rates were required in 12.5% of the cases because of early or late tPA failure. tPA appears to be as effective as urokinase for reestablishing adequate blood flow rates through hemodialysis catheters that are thrombosed or have low blood flow rates.