The influence of early postnatal socio-emotional deprivation on the development of tyrosine hydroxylase- and 5-hydroxytryptamine-immunoreactive fiber innervation in the medial prefrontal cortex was quantitatively investigated in the precocial rodent Octodon degus. Forty-five-days-old degus from two groups were compared: (i) degus which were repeatedly separated from their mothers during the first three postnatal weeks and after weaning reared in complete isolation; and (ii) degus which were reared under normal undisturbed social conditions. The two monoaminergic fiber systems in the four subregions of the medial prefrontal cortex responded differentially to the deprivation. While the infralimbic cortex was the only subregion that displayed an increase in 5-hydroxytryptamine-positive fiber densities (129.2%) but no changes in tyrosine hydroxylase-immunoreactive fibers, the precentral medial (82.2%), anterior cingulate (74.6%) and prelimbic cortex (86.9%) showed significantly reduced tyrosine hydroxylase-positive fiber innervation, but no changes in 5-hydroxytryptamine-immunoreactive fiber densities. The number of tyrosine hydroxylase-positive somata in the ventral tegmental area and in the substantia nigra remained unchanged. In cortical areas the number of tyrosine hydroxylase-immunoreactive somata was increased (depending on the medial prefrontal cortex subregion between 241.8% and 398.7%) in deprived animals. This altered balance between the serotonergic and dopaminergic cortical innervation in the different subregions of the medial prefrontal cortex may reflect a counter-regulative anatomical and functional adaptation, which may be triggered by an altered activity of these transmitter systems during the phases of maternal separation and social isolation.