Several aspects of the central regulation of respiratory control have been investigated on brainstem-spinal cord preparations isolated from newborn rats whose dam was given 0.02% caffeine in water as drinking fluid during the whole period of pregnancy. Analysis of the central respiratory drive estimated by the recording of C4 ventral root activity was correlated to Fos pontomedullary expression. Under normoxic conditions, preparations obtained from the caffeine-treated group of animals displayed a higher respiratory frequency than observed in the control group (9.2 Ϯ 0.5 versus 7.2 Ϯ 0.6 burst/min). A parallel Fos detection tends to indicate that the changes of the respiratory rhythm may be due to a decrease in neuronal activity of medullary structures such as the ventrolateral subdivision of the solitary tract, the area postrema, and the nucleus raphe obscurus. Under hypoxic conditions, the preparations displayed a typical hypoxic respiratory depression associated with changes in the medullary Fos expression pattern. In addition, the hypoxic respiratory depression is clearly emphasized after in utero exposure to caffeine and coincides with an increased Fos expression in the area postrema and nucleus raphe obscurus, two structures in which it is not increased in the absence of caffeine. Taken together, these results support the idea that in utero caffeine exposure could affect central respiratory control. Caffeine, which belongs to the methylxanthine family, is commonly ingested in various beverages such as coffee, tea, or cola drink (1). It interacts with adenosine neuronal transmitter system as an A 1 and A 2A receptor antagonist (2) and has been shown to alter the adenosinergic transmission upon chronic administration (3-5).In rats, a positive correlation has been established between exposure to caffeine during gestation and a reduction of the fetal cerebral weight (6). Such an observation could lead to propose that caffeine modifies maturational neuronal processes. Moreover, various studies reported that a sustained maternal caffeine intake induces harmful physiologic effects on human newborns (for review, see 7). Among these effects, respiratory perturbations have been described (8 -10). Nevertheless, the existence of a relation between exposure to caffeine during pregnancy and the occurrence of respiratory perturbations in