Background: For many years, researchers and clinicians have described parent reports of an unusual developmental phenomenon in a substantial minority of children with Autistic Spectrum Disorders (ASD), the acquisition and then loss of communication skills during the second year of life. Methods: As part of a longitudinal study of 110 children referred for assessments of possible autism at age 2 years or younger, 21 developmentally delayed children and 33 typically developing controls, 19 children were described by their parents at age 2 as having gained and lost spontaneous, meaningful words, and 12 children as having a history of less specific loss of imitated words or nonword vocalizations. A battery of diagnostic and cognitive tasks was administered to all children at study entrance, at ages 3 (for the referral children only) and 4 or 5 (for referral and developmentally delayed children). Results: Results indicated that the acquisition of a small number of spontaneous words used meaningfully and consistently followed by loss of all words, often associated with other social changes, was unique to children diagnosed at 5 years with ASD. Few differences, besides those that defined the pattern of word loss, emerged between children with ASD with and without word loss. Loss of less specific, nonword vocalizations was associated with cognitive delay, with or without autism. Conclusions: Word loss is a reliably identifiable phenomenon in early childhood that appears to be unique, but not universal to, ASD. Histories and outcome of children with word loss were not in keeping with a sudden change from normal to abnormal functioning, but did suggest that this type of loss in the second year of life may be a useful "red flag" for ASD in a significant minority of cases.