Periodic breathing (PB) has been considered a benign respiratory pattern in preterm infants, but the ventilatory changes associated with this respiratory pattern, especially in small and very inmature infants (≤1500 g), has not been studied. To test the hypothesis that PB is associated with significant decreases in ventilation and O2 saturation in infants ≤1500 g, we studied 18 healthy preterm infants. Of these, 11 were ≤1500 g [birthweight 1.1±0.1 kg (mean±SE), gestational age 29±1 wk, postnatal age 19±4 d] and 7 were >1500 [birthweight 1.7±0.1 kg, gestational age 31±1 wk, postnatal age 25±4 d]. We measured ventilation using a flow-through system. A total of 75 epochs of periodic breathing were analyzed (37 in group ≤1500 g and 38 in group >1500 g). In infants ≤1500 g ventilation decreased from 0.215 ± 0.015 1·min-1·kg-1 before PB (control) to 0.179 ± 0.024 (16%; p<0.0001), compared with a decrease from 0.181 ± 0.008 to 0.173 ± 0.005 1·min-1·kg-1 in the group> 1500 g (1%; p=NS). Maximal decrease in ventilation (cycle with lowest ventilation) occurred sooner (47 ± 10 s) and was more pronounced (38%) in the group ≤1500 g than in the group >1500 g (96 ± 30 s; 21%; p<0.001 for both). In infants ≤1500 g O2 sat decreased from 92± 1% before to 80 ± 1% during the apneic period (p<0.0001). The% change in O2 saturation before and after the periodic apnea was also greater in the group ≤1500 g (18% vs 4%; p<0.0001). These findings suggest that in infants ≤1500 g: 1) PB is associated with significant decrease in ventilation and O2 desaturation and; 2) there is a more pronounced and faster decrease in ventilation than in the more mature infants. We speculate that PB in infants ≤1500 g is per se a deleterious respiratory pattern leading to significant decrease in ventilation and desaturation.Supported by the Children's Hospital of Winnipeg Research Foundation.