The use of continuous, low-dose heparin in total parenteral nutrition (TPN) formulas to limit central venous thrombosis was retrospectively evaluated. Seven of 129 patients (5.4%) developed central vein thrombosis when TPN solutions provided less than 6,000 units (usually 1,000 units/liter) heparin per day. In the subsequent period when heparin was increased to 6,000 units per day, 10 of 858 (less than 1.2%) patients developed a TPN-related thrombosis (P less than 0.0005). The incidence of antithrombin III (AT III) deficiency in a subset of high-risk patients scheduled to receive TPN was 51% (23 of 55). Twelve of the 23 had clinical evidence of thrombosis, whereas only 3 of 22 patients with normal AT III levels did (P less than 0.01) A major contributing factor to the development of thrombosis in TPN appears to be depression in antithrombin III levels, which is commonly found in patients who require this therapy. Low-dose heparin appears to reduce the incidence of thrombosis with TPN when provided continuously in sufficient amounts.