An in vitro assay to test for regional differences in neurite growth-promoting and growth-inhibiting factors in tissue sections of CNS tissue has been adapted to the use of postmortem human brain tissue. Frozen sections of the temporal lobe from victims of Alzheimer's disease were used as substrates for sympathetic neurite outgrowth in tissue culture. Tissue sections from a non-Alzheimer's brain were used as a control. Both explanted chick sympathetic ganglia and dissociated chick sympathetic neurons were cultured for 3 to 5 days on tissue sections in the presence of exogenous nerve growth factor. The dichotomy between gray and white matter portions of the tissue sections in supporting neurite outgrowth that was previously reported for fresh frozen human brain tissue was also found to persist in postmortem tissue. In addition, the total neurite outgrowth from explanted sympathetic ganglia was found to be significantly less on postmortem sections when compared with previous results obtained from fresh frozen tissue samples of epileptic tissue. Dissociated neurons exhibited neurite outgrowth on Alzheimer's sections that showed preferential growth on blood vessel segments but no affinity for senile plaques. The results suggest that there is some decline in the neurite growth-promoting ability of cortical gray matter obtained from postmortem-derived brains when compared with fresh tissue and that senile plaques do not represent sites of neurite stimulation in this in vitro system.