Fas mediated apoptosis, and the apoptosis related Fas receptor and bcl-2 protein were investigated in peripheral blood lymphocytes from patients with extensive leukemic cutaneous T cell lymphoma (CTCL).Fas receptor and bcl-2 protein expression were measured by flow cytometry. Fas mediated apoptosis was induced by cross linking with monoclonal anti-Fas antibody for 15 hours and quantitated by flow cytometry using DNA terminal dUTP nick end labeling (TUNEL) assay. Changes in bcl-2 protein were measured after cross linking for 15 hours with monoclonal αCD3ε, αUCHL1 (CD45RO), or αGAP 8-3 (CD45) independently or after cocultivation of αCD3ε, and either αUCHL1 or αGAP 8-3. The bcl-2 expression was also investigated following 1 wk. culture.Fas expression ranged from normal (mean channel florescence [MCF]=1 0.21) to elevated levels (MCF 1.73). Far cross linking did not result in apoptosis. Stimulation through the CD45 receptor alone or through CD45 + CD3 resulted in bcl-2 protein increase (2 increase). The bcl-2 increase was greater using antibody to the CD45RO idiotype than with GAP 8-3. Culture of CTCL caused a progressive loss of bcl-2 protein with spontaneous apoptosis occurring at one week.CTCL cells may be protected from apoptosis by the expression of bcl-2 protein. In vitro, there is progressive loss of the bcl-2 protein unless the CD45RO receptor is stimulated. These results may indicate why CTCL cells do not grow well in vitro and may provide a mechanism for the unregulated growth of the neoplasm in vitro.