Increases in beta-amyloid precursor proteins (APP), which include the beta-amyloid senile plaque protein present in patients with Alzheimer's disease, have been shown to occur in models of neuronal damage and neurotoxic cell injury. This observation led us to examine the expression of these proteins after transient ischaemic episodes in the gerbil. Animals were killed 2-28 days after ischaemia and APP were detected by immunocytochemistry at the light and electron microscopic levels with an antibody raised against the C-terminal region of these proteins. The gliotic reaction was also examined using glial fibrillary acid protein (GFAP) immunoreactivity. Two days after ischaemia, neuronal cell death was observed in the hippocampal CA1 region accompanied by astrocyte hypertrophy. These hypertrophic astrocytes were found to be GFAP positive but stained weakly for APP. Seven days after ischaemia both astrocyte hypertrophia and hyperplasia, with identified mitotic figures, were observed. These hyperplasic astrocytes were intensely stained by the APP antibody, and were observed up to 28 days after ischaemia. This shows that neuronal cell death produced by transient ischaemia is followed by an increased APP expression which appears to be associated with the hyperplasic astrocytes but not with the initial hypertrophy of this cell population. These results, when taken together with those obtained in other models of neuronal damage or death, clearly suggest that APP expression follows neuronal death and is associated with astrocyte proliferation.