Oncostatin-M is a cytokine produced by macrophages and activated T lymphocytes that has recently been shown to be a mitogen for AIDS-related Kaposi's sarcoma (KS)-derived spindle cells. The significance of oncostatin-M production in AIDS-related KS in vivo, however, remains unknown. In this study we wanted to determine whether oncostatin-M is expressed in vivo in patients with HIV-I-related KS, define the cell types that express this cytokine, and compared with the control tissues from HIV-I-negative individuals. A second objective of our study was to define the expression of oncostatin-M in AIDS-KS-derived spindle cell isolates cultured in vitro and to determine whether oncostatin-M is an autocrine growth factor for these KS cells. We have determined that oncostatin-M is not expressed in any of the several organs examined in control cases, whereas the tumor tissue obtained from the skin biopsies of HIV-I-infected cases with KS displayed oncostatin-M expression in the spindle cell components of the tumor, as well as the cells lining the vascular structures, smooth muscle cells lining the eccrine sweat glands, and the epidermal layers of the skin. Furthermore, uninvolved skin of patients with HIV-related KS express oncostatin-M in the cells lining normal vessels. The mRNA polymerase chain reaction analysis confirmed findings in the primary tissues and showed expression in all of the AIDS-KS-derived spindle cell isolates examined. We have also shown with the use of oncostatin-M-specific antisense oligodeoxynucleotides that KS cell proliferation is inhibited, which correlated with a more precipitous decline in the production of interleukin-6 by these cells. We conclude that oncostatin-M is only expressed in the skin and KS tumor of HIV-I-infected individuals. Furthermore, we provide evidence that oncostatin-M is an autocrine growth factor for KS.