There are some doubts whether in a severe renal failure the dose of alteplase should not be modified, especially when its plasma clearance may be decreased by liver ischemia. The authors present a case of a 67-year old woman with massive pulmonary embolism (PE) and acute renal failure (creatinine 580 micromol/l) of a mixed etiology (renal calculosis with hydronephrosis and shock as PE presentation). Alteplase administration (10 mg bolus followed by reduced to 50 mg two hours infusion) resulted in hemodynamic stabilization but was complicated by gross subcutaneous hematomas, intensive epistaxis and hematuria, and hemoglobin decrease which required blood transfusions.