Caffeine, which belongs to the methylxantine family of compounds, is commonly ingested in a range of beverages such as coffee, tea, and cola drinks. It is also used therapeutically and is frequently employed in the treatment of respiratory disturbances in human neonates. The aim of the present work has been to examine the ontogeny of the adenosine A1 receptor system in the brainstem of the newborn rat following postnatal treatment with caffeine to mimic the therapeutic administration of caffeine to premature human infants. The effect of this postnatal exposure to caffeine on the gradual appearance of adenosine A1 receptors was analysed by determining immunohistochemically the distribution of the receptors. The main difference between control animals and animals exposed to caffeine was the transient increase (only at postnatal day 6) in the number of immunopositive neurons in two brainstem areas, the ventrolateral medulla and the rostral dorsolateral pons, in caffeine-treated rat pups, or more specifically, the parabrachial and K?ker-Fuse nuclei, both of which are classically associated with respiratory control. With previous research highlighting the important role played by the rostral pons in respiratory modulation by the adenosine A1 receptor system, it is thus possible that postnatal exposure to caffeine modulates the ontogeny of the adenosine A1 receptor network. This could imply that the role of caffeine to decrease the incidence of neonatal respiratory disturbances may be due to the earlier than normal development of the adenosinergic system in the brain.