Previous studies showed that early environmental conditions severely affect the morphology of the granule cells in the hippocampal dentate gyrus and pyramidal neurons in fields CA3 and CA1. The aim of the present study was to determine whether early isolation affects neuron morphology in layer II of the entorhinal cortex, from which the perforant path to the dentate gyrus and CA3 takes its origin. Male and female guinea pigs were assigned at 6-7 days of age to either a control (social) or an isolated environment where they remained for 80-90 days. The brains were Golgi-Cox stained and neurons were sampled from layer II of the entorhinal cortex. Morphometric analysis was carried out on star cells, the most abundant neuron population. Isolated males had star cells with less dendritic branches, a shorter dendritic length and a smaller dendritic spine density than control males. In contrast, isolated females had more dendritic branches than control females, though this difference was of small magnitude. While isolated males had star cells with a smaller soma than control males, isolated females had a soma larger than control females. In both environments sex differences were found in the star cell morphology. In the control environment males had more dendritic branches, a greater dendritic length, a larger soma but a smaller spine density than females. In the isolated environment males had less branches, a shorter dendritic length, a smaller spine density and a smaller soma than females. The results indicate that early isolation affects the structure of the star cells in the entorhinal cortex and that males and females react to isolation in an opposite manner. A similar sexually dimorphic response to early isolation was previously observed in the dentate gyrus and fields CA3 and CA1. The presence of widespread effects of isolation in the entorhinal cortex and numerous hippocampal structures suggests that the outcome of early isolation might be a change in learning and memory functions requiring the hippocampal region.