In 132 soft-tissue sarcomas and 52 benign soft-tissue tumors, cellular proliferation was examined by immunohistochemistry using monoclonal antibodies Ki-S11 (Ki-67 antigen) and Ki-S1 (topoisomerase II alpha) and by flow cytometric analysis of the S-phase fraction (SPF). Malignant tumors were graded histologically according to the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system. Patient age, sex, tumor location, histological type, and DNA ploidy were considered as additional prognostic variables. Consistent immunoreactivity was seen in approximately 95% of the cases, and determination of SPF was possible in approximately 60% Ki-S11 and Ki-S1 immunolabeling indices correlated in a linear manner. All proliferation parameters yielded significant differences between benign and malignant tumors. Ki-S11 and Ki-S1 immunoreactive scores also co-varied significantly with SPF, mitotic count, and histopathological grade. In univariate analysis, immunohistochemical proliferation indices, histopathological grade, mitotic count, and SPF were predictive of overall survival and the development of metastases. In multivariate analysis, immunolabeling scores of proliferation markers, grade, and SPF emerged as independent predictors of global survival and systemic progression. We conclude that the immunohistochemical assessment of proliferation, being more readily performable and more easily assessable than the equally relevant S phase fraction, may add appreciable information to the current prognostic models for soft-tissue sarcoma.