Low density cell cultures of embryonic rat hippocampus containing astrocyte-like glia and neurons were used to test the hypothesis that glia can alter 'natural' and excitatory amino acid (EAA)-induced neuronal death. Neurons contacting glia survived for longer time periods than did neurons not contacting glia. Neurons associated with glia were also protected against glutamate and kainate neurotoxicity. Fibroblast growth factor (FGF)-like immunoreactivity was associated with the glia. Addition to the cultures of an antiserum raised against an internal peptide fragment of FGF greatly reduced the protective effect of glia against both spontaneous and EAA-induced neurotoxicity. Contact with glia, or exposure to exogenous FGF, also protected the hippocampal neurons against Ca2+ ionophore-induced degeneration indicating that FGF enhanced the ability of neurons to handle a Ca2+ load. Taken together, these results suggest that glia surface-associated FGF may play important roles in hippocampal development, and in neurodegenerative conditions that involve EAAs.