Human lung adenocarcinoma A549 cells and cisplatin-resistant A549/DDP cells were treated with clinically relevant doses of cisplatin (30 μmol/L) and then further cultured under the same conditions. DNAs of both cell lines were extracted and subjected separately to agarose gel electrophoresis. Results showed that DNA ladders could be seen in A549 cells cultured for 12 h, while no apoptotic character appeared in cisplatin-resistant A549/DDP cells even after being cultured for 48 hour. This difference between two cell lines was further confirmed by apoptotic peaks measured with flow cytometry. Biochemical and biophysical experiments indicated that the mitochondrial membrane potential and pH_i of cisplatin-sensitive A549 cells decreased significantly, whereas the intracellular free Ca²⁺ concentration increased greatly with the culture time. But the mitochondrial membrane potential and pH_i remained at a relatively high level and the intracellular free Ca²⁺ concentration was reduced gradually with the culture time for cisplatin-resistant A549/DDP cells. It would be suggested that the anti-apoptotic character of A549/DDP cells is related with the relative intracellular basification, the persistence of mitochondrial membrane potential and decrease in intracellular free Ca²⁺ concentration which would be responsible for the resistance of A549/DDP cells to cisplatin.