In order to clarify the role of both apoptosis and immunosuppressive cytokines in the pathogenesis of aplastic anaemia (AA), bone marrow (BM) condition in AA was simulated through long term bone marrow culture (LTBMC). Fourteen acquired aplastic anaemia (AAA) cases were included in the study .They were subjected to full history taking, clinical examination, and haematological laboratory investigations. LTBMCs were carried out for bone marrow aspirates of these cases, and were considered as Group I. LTBMCs were also carried out for 14 non-aplastic non-neoplastic bone marrow samples, in duplicates: 1) 14 non-aplastic non-neoplastic bone marrow LTBMCs to which supernatants of LTBMCs of GroupⅠ were added (GroupⅡ), 2) 14 non-aplastic non-neoplastic bone marrow LTBMCs that were carried out without addition of GroupⅠ culture supernatants (GroupⅢ), and were considered as a control for bothⅠ&Ⅱ. Apoptosis was estimated (using the TUNEL technicque) in cells/colony and colony/10 colonies in the culture supernatants of the three groups, and the three groups were compaired to each other according to the degree of apoptosis. The number of apoptotic cells/colony was significantly higher in LTMBCs of normal bone marrow to which supernatant from LTBMCs of AA were added, than in normal LTBMCs that were carried out without addition of aplastic LTBMCs supernatants (P=0.01). However, no significant difference was found in the number of apoptotic cells/colony between LTBMCs of AA & normal LTBMCs to which supernatants from LTBMCs of AA were added (P=0.29) ,or between LTBMCs of AA & normal LTBMCs that were carried out without addition of aplastic LTBMCs supernatants (P=0.59) .On the other hand, the difference in the number of apoptotic colonies/10 colonies was significantly higher in LTBMCs of AA than in normal bone marrow LTBMCs that were carried out without addition of aplastic LTBMCs supernatants (P= 0.004). The number of apoptotic colonies/10 colonies was also significantly higher in LTBMCs of AA than normal marrow LTBMCs to which supernatants of LTBMCs of AA were added (P=0.04), whereas no significant difference in the number of apoptotic colonies/10 colonies was found between normal bone marrow LTBMCs to which supernatants of LTBMCs of AA were added and normal bone marrow LTBMCs that were carried out without addition of aplastic LTBMCs supernatants (P= 0.27), suggesting a possible stem cell defect in aplastic anemia. Accordingly, we can conclude that two factors may contribute to the pathophysiology of aplastic anemia namely the increased apoptosis in stem cell compartment secondary to a primary stem cell defect, and increased immunosuppressive cytokines that contribute to the severe cytopenia.