Maternal caffeine intake has been suggested to influence the offspring. We have studied the effects of maternal caffeine intake on adenosine and GABA receptors, targets for caffeine, during development of the rat brain. Caffeine (0.3 g/L) was added to the drinking water of rat dams during pregnancy and early postnatal life. Adenosine A1 and A2A and GABAA receptor development was studied using receptor autoradiography and in situ hybridization. Pups were examined on embryonic d 14 (E14), E18, E21, 2 h after birth (P2h), P24h, postnatal d 3 (P3), P7, P14, and P21. Adenosine A, receptor mRNA was detected at E14 and receptors at E18. A1 mRNA levels increased from the level reached at E18 between P3 and P14 (maximally a doubling), whereas A, receptors, studied by [3H]-1,3-dipropyl-8-cyclopentyl xanthine binding, increased later and to a much larger extent (about 10-fold) postnatally. Caffeine treatment had no significant effect on adenosine A1 receptors or on A1 receptor mRNA. A2A mRNA had reached adult levels by E18, whereas receptor levels were low or undetectable before birth and increased dramatically until P14. Caffeine did not influence A2A receptors or A2A receptor mRNA at any stage during development. [3H]-flunitrazepam binding, representing GABAA receptors, showed large regional variations during ontogeny, but there were no clear differences between the caffeine-exposed and the nonexposed pups. Thus, exposure to a low dose of caffeine during gestation and postnatal life had only minor effects on development of adenosine A, and A2A receptors and GABAA receptors in the rat brain.