Several apoptosis-inducing systems, including Fas/Fas ligand and TNF-related apoptosis-inducing ligand (TRAIL) and its receptors, are upregulated in myelodysplastic syndrome (MDS). FLIP (FLICE (FAS-associated death-domain-like IL-1b-converting enzyme)-inhibitory protein)) was identified as an inhibitor of FAS and TRAIL signals. Here, we characterized FLIP Long (FLIP L ) and FLIP Short (FLIP S ) expression in bone marrow mononuclear cells (BMMNCs) and in CD34 þ cells of 29 MDS patients, and in 17 normal volunteers. The expression was correlated with apoptotic indices. In CD34 þ cells, FLIP L levels were higher among normal individuals than in MDS patients (P ¼ 0.04). Among total BMMNC, FLIP L levels also tended to be higher in normal subjects than in MDS patients, although this difference was not significant (P ¼ 0.71). FLIP L levels in CD34 þ cells were negatively correlated with apoptosis in both normal and MDS marrows (P ¼ 0.03). FLIP Short RNA expression was higher in MDS patients than in normal controls in both BMMNC (P ¼ 0.03) and CD34 þ cells (P ¼ 0.08). In contrast to FLIP L , FLIP St levels were positively correlated with apoptosis. At the protein level FLIP was most readily detectable in patients with high blast counts. The data suggest that FLIP L and FLIP S are differentially regulated, and that the relative levels of both isoforms play a role in the regulation of apoptosis in MDS.