The effects of various Ca2+ antagonists on lipid peroxidation in singlet O2-challenged isolated cardiomyocytes from adult rat heart were investigated. Singlet O2-challenged untreated cells all hypercontracted as a consequence of Ca2+ overload and produced 463.6 +/- 143.6 nM malondialdehyde (MDA; mean +/- SD, n = 8). Protective Ca2+ antagonists reduced the amount of damaged cells, but did generally not affect MDA production. On the other hand, free radical scavengers and antioxidants displayed a good correlation between number of protected cells and MDA produced. It is concluded that flunarizine-like Ca2+ antagonists protect cells against Ca2+ overload without, however, interfering with peroxidative processes.