Prenatal starvation causes pulmonary hypoplasia in newborn guinea pigs, and is associated with postnatal cyanosis, hypothermia, and respiratory failure. To determine the effects of such starvation on ventilation, neonates from litters either fed ad libitum throughout gestation (control) or given 50% rations in the last trimester of pregnancy (starved) were studied at 29 degrees C by plethysmography in 21, 11, and 5% O2. After 15 min (steady-state) in 11% and then 5% O2, 13 of 14 controls (mean = 95 g) sustained increases in weight-specific minute ventilation of 46 and 75% compared to values in air (p less than 0.01), due to increases in respiratory frequency. Seven of 11 starved neonates (mean = 76 g) also sustained increases in respiratory frequency and weight-specific minute ventilation in 11 and 5% O2 similar in magnitude to those of the normal controls, although at higher weight-specific tidal volumes. One abnormal control (85 g) and four starved neonates (mean = 70 g) hyperventilated in air, did not respond to 11% O2, and then hypoventilated in 5% O2 due to a reduced weight-specific tidal volume. Neonates with normal ventilatory patterns did not alter weight-specific minute ventilation in 100% O2 and did not show a biphasic response in acute (1-5 min) exposures to moderate hypoxia, as noted for newborn of other species. Thus, hypoxia identified those starved neonates in which pulmonary immaturity or other starvation-induced pathologies necessitated a maximal ventilatory effect in air. The sustainable hyperventilation among normal guinea pigs during hypoxia emphasizes the precocial development in this species at birth, which may be compromised by intrauterine starvation.