Patients with renal failure frequently manifest a hemorrhagic diathesis characterized by prolonged bleeding time (BT). Oral and intravenous estrogens have been shown to correct this abnormality, but both estrogens have real and potential disadvantages, especially for long-term use. We examined the effectiveness of transdermally applied 17 beta-estradiol on clinical bleeding and BT in renal failure patients. Six patients with renal insufficiency and prolonged BT were included in the study. Four patients had recurring gastrointestinal bleeding from telangiectasias. Two patients anticipated percutaneous renal biopsy. Transdermal estradiol 50 or 100 micrograms/24 hr was applied every 3.5 days for a period of 2 months. Bleeding times were measured just prior to estrogen administration (pre-estradiol) and again on cessation of clinical bleeding or prior to renal biopsy (post-estradiol). Differences were analyzed using a paired t-test. Erythrocyte transfusion requirement 2 months before and 2 months after estradiol application also was observed. Hemorrhage in all four actively bleeding patients ceased or improved, as reflected by the reduced need for transfusion. Bleeding time improved significantly (P = 0.008) when comparing before (day 0) with after (days 1 to 17) estradiol application. No adverse reactions associated with estradiol occurred over 2 months of therapy. In conclusion, transdermal application of 17 beta-estradiol is a safe and effective means to reduce BT and clinical hemorrhage in patients with renal failure and prolonged BT.