THE biological basis of the clinical efficacy of lithium in the treatment of mental illness has been extensively studied in neurones, but little is known about the effects of the drug on glia. Recently we showed that treatment of rats with clinically relevant doses of lithium chloride results in a 35% increase in the immunocontent of the astrocyte marker GFAP in the hippocampus. Here we studied the cytology of this phenomenon. Rats were treated for 4 weeks with a lithium diet which resulted in serum Li+concentrations of 0.6–1.2 mmol/l. GFAP immunocytochemistry of the hippocampus revealed a mild gliosis in the CA1 area and the dentate gyrus which was associated with a change in the orientation of astrocytic processes. In control animals astrocyte processes were mainly orientated perpendicular to the stratum pyramidale, whereas in treated animals the cells were predominantly stellar in appearance.