Although various nonrandomized evaluations of adjuvant chemotherapy have suggested that chemotherapy with doxorubicin-containing regimens is valuable in the adjuvant treatment of patients with high-grade soft tissue sarcomas, the varied nature of this disease makes it extremely difficult to draw definite conclusions from these studies. Recently several prospective randomized trials on the efficacy of adjuvant chemotherapy in these patients have been performed. Although trends toward improved disease-free survival were seen in several trials, these did not achieve statistical significance. Follow-up in these trials is short, however, and patients with sarcomas at diverse anatomical sites were combined in the analyses. In a series of prospective randomized trials conducted in the Surgery Branch of the NCI in conjunction with the Radiation Oncology and Medical Oncology Branches of the NCI, it appears that adjuvant chemotherapy with doxorubicin and cyclophosphamide is of major benefit in improving disease-free and overall survival in patients with high-grade soft tissue sarcomas of the extremities. Patients with truncal lesions occurring on the trunk wall also had a significant improvement in disease-free survival with adjuvant chemotherapy. We could, however, demonstrate no benefit for adjuvant chemotherapy in patients with retroperitoneal sarcomas, probably because of the extensive intra-abdominal spread of this tumor and the inability to excise these tumors with negative surgical margins. Toxicity due to the adjuvant chemotherapy is substantial, however, especially cardiomyopathy due to high cumulative doses of doxorubicin.(ABSTRACT TRUNCATED AT 400 WORDS)