The aim of this study was to develop a minimally invasive and reliable method for measuring peripheral chemoresponsiveness to oxygen in infants, and to establish baseline data from normal infants at 12 weeks of age. Two-breath alternations in fractional inspired oxygen (FI,O-2), switching between 0.42 to 0.00 were given for 2 min periods via a face mask (held close to the face but without contact) to 18 healthy infants during quiet sleep. End-tidal oxygen concentrations alternated between 21 and 11%, Instantaneous minute ventilation (V'E) and its components tidal volume (VT), respiratory frequency (fR) inspiratory and expiratory times (tI and tE), inspiratory flow (VT/tI), and inspiratory duty cycle (tI/t tot) were measured by respiratory inductance plethysmography. Two-breath alternations in each of the ventilatory components were matched with the corresponding alternating end-tidal oxygen record and compared with contiguous pre- and post-test data obtained in control periods of air breathing. Alternations in all ventilatory components except fR changed significantly during FI,O-2 alternations; VT 26%, tE -8%, VT/tI 18%, tI/t tot 11% and V'E 28% of baseline values. Within and between infant variances are reported for the individual components of ventilation. Differences among infants were best detected by alternations in V'E; within infant variance 76, between infant variance 171. We conclude that the test described is a safe, reliable and relatively easily applied method of measuring peripheral chemoresponsiveness, which is suitable for clinical application in infancy.