DVT involving the lower extremities is a frequent (25-40 percent of patients) complication of major thoracic, abdominal, and pelvic surgery in patients beyond the age of 40 years. Herein, we have reported a recently completed large prospective, randomized multicenter investigation of the prophylaxis of postoperative DVT in the United States. A total of 880 patients were randomized into five treatment groups: 0.5 mg of dihydroergotamine plus 5,000 IU of heparin (DHE/H5,000), 0.5 mg of dihydroergotamine plus 2,500 IU of heparin (DHE/H2,500), 5,000 IU of heparin alone (H5,000), 0.5 mg of dihydroergotamine alone (DHE), or placebo. Administration was by the subcutaneous route, using the anterior abdominal wall on a twice daily schedule. Treatment was initiated preoperatively and continued twice daily for 5 days. Daily radiofibrinogen uptake tests revealed the following DVT rates: DHE/H5,000 9.4 percent, DHE/H2,500 16.8 percent, H5,000 16.8 percent, DHE 19.4 percent, and placebo 24.4 percent. DHE/H5,000 was significantly superior (p less than 0.05) to all other treatments in this respect. Adverse drug experiences did not differ significantly between groups and consisted primarily of postoperative bleeding (2 to 3 percent of patients), injection site hematoma (6 to 12 percent of patients), and wound hematoma (1 to 3 percent of patients).