Apolipoprotein E (apoE) genotype is well known as a risk factor for Alzheimer's disease, but more recently also has been associated with the incidence or disease progression of other neurological diseases including amyotrophic lateral sclerosis (ALS). In the present study we have examined the distribution of apoE in the spinal cord of transgenic mice with a familial ALS-linked superoxide dismutase 1 (G93A-SOD1) mutation. Western immunoblotting and immunocytochemistry showed a strong increase in apoE expression in G93A-SOD1 mice coincident with the onset of paralysis (age > 24 weeks). Increased apoE expression occurred in astrocytes and throughout the neuropil. The increase in apoE expression closely correlated in time and spatial distribution with axonal and neuronal degeneration as determined with a silver staining procedure, consistent with a role as an 'injury-response' protein.