Most of the available data on the hypoxic ventilatory response (HVR) in infants has been obtained in quiet sleep (QS), and only one study has made repeated tests in the same infant. We aimed to gain a more complete knowledge of the maturation and consistency of the initial phase of the HVR by performing multiple tests in both QS and active sleep (AS) over the first 6 mo of life in term infants. Fifteen healthy term infants were studied with daytime polysomnography longitudinally at 2-5 wk, 2-3 mo, and 5-6 mo after birth. Each infant received multiple hypoxic (15% O2, balance N2) challenges (three or more) in both AS and QS. In AS, infants consistently aroused to hypoxia; however, in QS, infants both aroused and failed to arouse. The initial phase of the HVR varied considerably between infants with the changes in ventilation/kg [SD of inspired minute ventilation per kilogram of body weight (V(I)/kg)] being more variable during AS than QS at all three ages and overall decreasing with postnatal age in both sleep states. The variability between replicate V(I)/kg measurements was also significantly greater in AS compared with QS at 2-5 wk postnatal age. There was no evidence of habituation to repeated hypoxic tests in either sleep state. Our study has demonstrated that the initial phase of the HVR is variable both between and within term infants in both AS and QS, with responses being markedly more variable during AS, and becoming more consistent with increasing postnatal age. By performing only one test or by failing to account for arousal responses, previous studies may not have detected the natural variation of the infant HVR.