Extracellular ATP (ATPo) is capable of inducing different events on cells through receptor activation. The effect produced by ATPo was studied in the cell line K562 and its multidrug resistant (MDR) counterpart, Lucena 1. Lower ATPo concentrations (1 mM and 2.5 mM) led to high (3)H-thymidine incorporation but no increase in cell number. Similarly, the cell cycle profile indicated an increase of cells in S phase and a decrease in G1 and G2, suggesting that the cells did not duplicate their DNA content. Higher doses of ATP (5 mM and 10 mM), as well as UTP (5 mM) and the P2X(7) agonist BzATP, were cytotoxic. However, no expression of P2X(7) receptors could be detected by Western Blot nor were the cells permeabilised by ATP, suggesting that pore formation was not involved in cell death. Both ecto-ATPase and ecto-5'-nucleotidase activity could be demonstrated at the surfaces of K562 and Lucena 1 cells, the latter presenting a higher ecto-5'-nucleotidase activity. Adenosine induced cell death at lower concentrations (2.5 mM) on both cell lines. Furthermore, an increased number of dead cells could be observed when 5 mM Adenosine was used compared to the same concentrations of ATPo. It still remains to be elucidated the nature of the receptors involved in the induction of cell death in these cells.