Neuronal apoptosis has been described during development but little is known about whether apoptosis plays a role in neurodegenerative disease. Neurodegenerative cell death can be difficult to study because it is often a slow process and it is limited to only a few cells among many nondying cells. We used molecular methods to study cell death in the spinal cords of wobbler mice, a model of motoneuron disease, and compared it to retinas of rd mice, a model of retinitis pigmentosa, where it is known that photoreceptors die by apoptosis. Increased levels of mRNA of testosterone-repressed prostate message 2 (TRPM-2) were found in motoneurons of wobbler mice and the retinas of rd mice. In motoneurons, TRPM-2 mRNA colocalized with increased expression of the message for growth-associated protein (GAP-43). In rd retinas, TRPM-2 mRNA was localized to ganglion cells of the inner retina known to survive the disease. These suggest that TRPM-2 expression is associated with cell membrane remodeling in surviving cells associated with synaptic reorganization or change in afferent input. In situ labeling of fragmented DNA (TUNEL staining) identified dying photoreceptors in the rd mouse. In the wobbler spinal cords dying motoneurons were not labeled. These data suggest that the process of neurodegenerative motoneuron cell death in wobbler mice is different from the apoptotic process of rd photoreceptors.