Five experiments that induced postnatal iron overload in mice are described. In Experiment I, exposure of NMRI mice to different doses (iron succinate: 0.0, 3.7 or 37.0 mg Fe2+/kg b. w., p.o.) on postnatal days (PD) 10—PD12 indicated marked disruptions of spontaneous motor behaviour and habituation in the 37.0 mg Fe2+/kg dose group, and to a lesser extent the 3.7 mg Fe2+/kg dose group. Analysis of brain iron content indicated significantly more total iron (μg/g) in the basal ganglia, but not frontal cortex of the higher, 37 mg/kg, dose group. In Experiment II, newborn NMRI mice were administered Fe2+ (7.5 mg/kg, b.w.) at either PD 3–5, PD 10–12 or PD 19–21, or vehicle (saline). Marked deficits in spontaneous motor behaviour and habituation were obtained in the mice administered iron during PD 10–12, and to a much lesser extent at PD 3–5. Analysis of total brain iron content indicated significantly more iron (mg/g) in the basal ganglia, but not frontal cortex of mice from PD 3–5 and PD 10–12 Fe2+ treatment groups. In Experiment III, the interactive effects of postnatal iron overload and administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to adult C57 BL/6 mice were examined by postnatal administration of iron (Fe2+) 7.5 mg/kg, b. wt., p.o. or vehicle (saline) at PD 10–12 followed, at 3-months of age, by administration of either MPTP (2 × 20 or 2 × 40 mg/kg, s.c.) or saline. Postnatal Fe2+ (7.5 mg/kg) caused drastic disruptions of spontaneous motor activity and habituation at behavioural testing (4-months age), and adult MPTP treatment potentiated these disruptions. Neurochemical deficits in dopamine (DA) and its metabolites (dihydroxyphenylacetic acid, DOPAC; homovanillic acid, HVA) induced by MPTP treatment were exacerbated by prior postnatal administration of Fe2+. The analysis of total iron content (mg/g) in brain regions indicated notably elevated levels in the basal ganglia, but not in the frontal cortex of mice administered Fe2+ at PD 10–12. MPTP-treated mice displayed severe depletions of DA, DOPAC and HVA in both the striatal and frontal cortical regions, i.e. Veh-MPTP40 as well as Fe-MPTP20 and Fe-MPTP40 groups, compared to the saline-treated (Vehicle) mice at 4-months of age, with lesser depletions by the Veh-MPTP20 group. In Experiment IV it was indicated that postnatal iron induced marked deficits (hypoactivity), initially, in all three parameters of motor activity at the 5.0 and 7.5 mg/kg doses, and to a lesser extent at the 2.5 mg/kg dose. Later combination with MPTP (2 × 40 mg/kg) potentiated severely these deficits. During the final period of testing a marked hyperactivity was obtained for the two higher dose groups; this effect was abolished in mice administered MPTP. In Experiment V, postnatal iron-induced deficits were alleviated in a dose-related manner by co-administration of the uncompetitive glutamate receptor antagonist, dizolcipine (MK-801), with a subthreshold dose of L-Dopa. Iron-overload during the immediate postnatal period seems detrimental for several aspects of functional and neurobiological development.