The apoptosis of blast cells in peripheral blood (PB) and bone marrow (BM) in leukemia during treatment, is of great interest. In recent studies, using the apoptotic index of the percentage of Circulating Apoptotic Cells (CAC) the newly diagnosed cases, 96 hours after the initiation of treatment, were distinguished in three groups: Group A had negligible CAC (<2%), which indicates rapid and successful apoptotic action of chemotherapy, group B had CAC between 6% and 12%, which indicates a more prolonged apoptotic action of chemotherapy and group C had high CAC (>20%). In the present study, the genes related to apoptosis and resistance to treatment are being evaluated in vivo, correlating the chemotherapy-induced apoptosis with the expression of p53, bcl-2, fas and mdr-1. These genes were studied immunocytochemically in BM and PB smears of 36 children with newly diagnosed leukemia. Apoptosis was studied in these cases by a nuclear staining method, directly in PB samples during the induction therapy. It was found that 19/36 cases belong to the group A and 11/36 cases belong to the group B. 6/36 cases belong to the group C, five of which failed to accomplish remission. The immunocytochemical analysis showed that 8/36 cases were positive for p53, out of which 7 (88%) belong to group A and 1 belong to group C. Bcl-2 positivity was found in 6/36 cases, out of which 3 belong to group B and 3 belong to group C. Fas positivity was detected in 6/36 cases, out of which 3 belong to group A, 2 belong to group B and 1 belongs to group C. Finally, all the mdr-1 positive cases (3/36) belong to group C. These results indicate that the rapid stimulation of chemotherapy-induced apoptosis depends on the p53 and fas expression, while the apoptosis retardation and resistance to treatment depend on the bcl-2 and mdr-1 expression.