Tacrolimus (FK506) and cyclosporin A (CsA) are immunosuppressants commonly used in transplantology. Their neuroprotective actions have also frequently been reported. Unfortunately, after prolonged administration, the drugs have numerous negative neurological side-effects which could also be observed in paediatric clinical cases. Since the problem has never been explored experimentally, the present study focuses on FK506 and CsA influence on the developing rat brain. Six- and 30-day-old rats (P6s and P30s, respectively) received two injections of FK506 or CsA, at a 24-hr interval. Control rats were injected with vehicle alone (Cremophor and ethanol mixture). When the rats were 60-day-old, weights and sizes of their brains were recorded. Additionally, quantitative assessment of calretinin-(CR+) and parvalbumin-immunopositive (PV+) inhibitory neurons was performed. In comparison to naive or vehicle-injected controls, FK506 or CsA-treated P6s showed decreases in the brain weight. In P30s, a decrease in the brain weight was observed only following the vehicle injections. In P6s, CsA injections reduced both CR+ and PV+ neuronal populations while FK506 injections reduced only numbers of PV+ neurons. In P30s, injections of the vehicle alone, but not those of FK506 or CsA, led to significant reductions of the CR+ and PV+ neurons. Generally, the results suggest negative long-term effects of FK506 or CsA on the developing brain. Interestingly, the negative effects of the vehicle were much stronger.