To define respiratory effects of peripheral acidemia during early development, we injected lactic acid (LA) into the jugular vein of 32 1- to 7-d-old rabbit pups and four adult rabbits. The body weight of newborns varied between 67 +/- 17 g in 1-d-old and 119.8 +/- 33.7 g in 7-d-old animals versus 4 +/- 0.1 kg in adults. Animals were anesthetized with ketamine (30 mg/kg) and urethane (0.6-1.2 g/kg), tracheotomized, and breathed spontaneously. Diaphragmatic electromyogram, tidal volume, esophageal pressure, and arterial pressure were recorded. In adult rabbits, a LA dose of 0.25 mM/kg elicited an increase in the rate of breathing with no change or a decrease in tidal volume (early response), followed by a deep and fast respiration (late response). The same LA dose had no effect or provoked only the late response in 1- and 2-d-old rabbits and led to the early and late responses in older newborns. The early response was abolished and the late response was diminished after vagotomy. Our results suggest that the early response is mediated by vagal afferents and the late response, although modified by vagal input, is of an extravagal origin. It is suggested that acidemia may be involved in the transient tachypnea syndrome in newborn infants. Possible contribution of vagal nonmyelinated endings in triggering the early response to LA is discussed.