Reactive oxygen species (ROS) are toxic for cells. BCL-2 is known as the anti-death protein and acts as an antioxidant. When the BCL-2 level of normal fibroblasts was suppressed by antisense bcl-2 oligodeoxynucleotide or antisense bcl-2 RNA expression, the life span of the culture was shortened by about 11 population doublings (approx. 15% of the total life span) in comparison to the control culture. Since about twice as many cell deaths were observed in the antisense culture than in the vector culture, the life span shortening was probably caused by ROS-induced death. Acceleration of telomere shortening was not evident in the antisense culture. Other BCL-2 family proteins showed no significant change in expression. Cell death was suppressed by N-acetyl-L-cysteine, an antioxidant, suggesting that ROS were the major cause of cell death. In conclusion, reduction of BCL-2 makes cells more sensitive to death induced by ROS and leads to shortening of the culture's life span.