Sequential measurements of the ventilatory response to a single breath of oxygen delivered during quiet sleep were made in 16 healthy infants between 1 and 3 months of age, alternately breathing air and 16% oxygen in nitrogen. At 1 month the response to a single breath of oxygen during normoxia was a decrease in minute ventilation of 264 +/- 34.2 (SEM) ml.min-1 during the 10-s period following the stimulus (p less than 0.001). During mild hypoxia the decrease in ventilation averaged 471 +/- 49.1 (SEM) ml.min-1 (p less than 0.001). The difference in response between measurements in air and mild hypoxia was significant (p less than 0.001). By the age of 3 months, the absolute ventilatory response to a single breath of oxygen increased significantly in normoxia by 118 +/- 35.2 ml.min-1 (p less than 0.01); the test response to breathing 16% oxygen paralleled the response to normoxia and was on average 254 +/- 26.6 ml.min-1 larger than the response when breathing air (p less than 0.001). When the three age groups were compared, calculating the response per killigram body weight showed that the response was similar at all three ages tested. These data provide a reference baseline for normal infants.