Neural cell degeneration underlies central and peripheral nervous system disorders. In this study we examined the influence of oxidized low density lipoprotein (Ox-LDL) on rat dorsal root ganglion (DRG) cells in culture. Methods used were cell morphology, lactate dehydrogenase (LDH) release, the TUNEL-reaction and DNA fragmentation. Exposure of DRG cells to Ox-LDL for 24 h led to elevation of LDH in the culture medium; short term exposure (4 h) induced apoptosis, evidenced by DNA fragmentation and a positive TUNEL-reaction. DRG cells modified LDL in the presence of Cu2+ to mildly oxidized and to a small extent to fully oxidized forms; these in situ-generated LDL oxidation products were strongly toxic. These results suggest that Ox-LDL is a neurotoxin; it initiates apoptotic cell injury which progresses to necrosis and cell death.