In mammals, perception of smells during the first hours of life is an essential prerequisite for adaptation of the newborn to the new extrauterine world. Functional magnetic resonance studies have shown that olfactory impression is processed in the lateral and anterior orbito-frontal gyri of the frontal lobe. Near-infrared spectroscopy (NIRS) can detect changes in oxygenated [Hb O2], and deoxygenated [Hb H] Hb during cortical activation. The aim of this study was to assess by NIRS olfactory cortex activity in newborn infants receiving olfactory stimuli. Twelve males and 11 females were studied when awake at 6 h to 8 d after birth. NIRS monitoring was carried out using two optodes placed above the left anterior orbito-frontal gyri. Each newborn was exposed for 30 s to two different smell stimuli-mother's colostrum and vanilla-and to a negative control, distilled water. Changes in Hb concentration were measured over the orbitofrontal region. During exposure to vanilla, [Hb O2] increased significantly over the left orbito-frontal area in all babies. The magnitude of the [Hb O2] increase over the illuminated region during colostrum exposure was inversely related to postnatal age. We conclude that monitoring Hb changes by NIRS can be valuable in assessing olfactory responsiveness in infants.