The response of astrocytes to pharmacological alterations of the serotonin (5-HT) content of the dorsal area dentata was studied by immunocytochemistry for S100 beta. Stereological analysis revealed changes in the density of astrocytic elements in conditions of 5-HT depletion and elevated 5-HT levels. There was a direct relationship between the expression of S100 beta and the level of 5-HT in the hippocampal formation. Thus when 5-HT was reduced by PCPA treatment, S100 beta immunoreactivity was also reduced. The converse of these observations was obtained in cases where the 5-HT levels were increased by fluoxetine administration. These immunocytochemical data are consistent with previous reports of the response of astrocytes to 5-HT in vitro.