Many neurons in the CNS die as a consequence of normal development. As these neurons die, they may be programmed to produce 'death proteins'. We explored the possibility that an antigen recognized by ALZ-50, a protein expressed in Alzheimer's-type neurofibrillary tangles, is generated during the process of neuronal death. The effects of transecting the infraorbital nerve on the expression of ALZ-50 immunoreactivity and neuronal death in the principal sensory nucleus of the trigeminal nerve (PSN) was examined. In normal rats, a small number of PSN neurons was ALZ-50-positive on postnatal day (P) 3. Transections on the day of birth (i.e. during the period of naturally occurring neuronal death) led to a 5-fold increase in the number of immunoreactive neurons expressing a 56-kDa protein on P3. In contrast, lesions on P25 (i.e. after the period of naturally occurring neuronal death) did not induce any neurons to exhibit ALZ-50 immunoreactivity. Thus, the 56-kDa protein recognized by ALZ-50 appears to be a death protein which is transiently expressed during the period of naturally occurring neuronal death. It is appealing to speculate that the pathological degeneration described in Alzheimer's brains results from the up-regulation of a quiescent developmental program.