We have studied the effect of excitatory amino acids on the expression of mRNA for the immediate early genes c-fos, c-jun, jun-B, and NGF-1A in isolated cortical astrocytes. The expression of the different genes was induced by 100 microM kainate, quisqualate, AMPA and high concentrations of K+ (140 mM). NMDA did not induce the expression of any of the genes studied. The effect of quisqualate stimulation was not inhibited by the antagonist CNQX or by withdrawal of external Ca2+. In contrast the kainate effect was abolished by CNQX but not by the removal of external Ca2+. However, elevated K+ induced c-fos only when calcium was present in the external medium. These findings suggest that type-1 astrocytes lack NMDA receptors and that the induction of genes by quisqualate and kainate is in part independent of the presence of calcium in the external medium and may be mediated through second messenger pathways.