We studied the effect of chronic psychosocial stress on cell death and volume changes in the tree shrew hippocampus. In situ end labelling (ISEL) identified low frequent but convincing apoptosis in many hippocampal subregions. Also in entorhinal cortex, apoptosis was found, generally at higher frequencies. After 28 days of chronic stress, apoptosis was significantly reduced in the CA1 stratum radiatum, whereas an increase was observed in the hilus (P < 0.04). With all subregions taken together, the hippocampus showed a decrease, whereas in the cortex, an increase in apoptosis was found after stress (P < 0.04). In a parallel and similar chronic stress study, post mortem morphometry of the same brain regions was performed, revealing mild decreases (7.6%) in entire hippocampal volume. We conclude that (i) low frequent apoptosis occurs throughout the adult tree shrew brain, and (ii) 28 days of chronic stress differentially affects its occurrence in distinct hippocampal subregions and entorhinal cortex. As previous stereological investigations failed to detect any loss in the principal neuronal layers, psychosocial stress, therefore, must affect other (structural) parameters like dendritic tree, interneurons, neurogenesis, or glia.