The objective of the present study was to confirm the link between spontaneous smiling and active sleep in newborns, and to identify the role of the cortex in the generation of spontaneous smiles. A total of 12 healthy newborns born at term and three infants with major congenital abnormalities (two with hydranencephaly and one with a left hemispherectomy) were evaluated by video and polysomnography during a 3-hr sleep period. Smiles were graded and their association with isolated rapid eye movements and grouped rapid eye movements was analysed. In all, 383 smiles were recorded of which 377 occurred during active sleep. Smiles were shown to be significantly associated with active sleep (p <.0001) and with grouped rapid eye movements (p <.0001). Bilateral smiles were more frequent than asymmetrical smiles. Among asymmetrical smiles, left-sided smiles were more frequent than right-sided smiles (p <.0001). Maternal stimulation during active sleep did not increase smiles. Smiling was absent during active sleep only in the infant with total hydranencephaly in whom nearly all cortical tissue was absent. In conclusion, smiling occurs in healthy newborns, almost exclusively in active sleep and is associated with grouped rapid eye movements. In infants with major congenital abnormalities, smiling is abolished only when nearly all of the cerebral cortex is absent. These results support the hypothesis of the role of active sleep in the stimulation of neuronal circuits responsible for spontaneous smiling and emphasise the importance of cortical areas in newborn smiling.