The Autism Mental Status Examination (AMSE) described here is an eight-item observational assessment that prompts the observation and recording of signs and symptoms of autism spectrum disorders (ASD). The AMSE is intended to take place seamlessly in the context of a clinical exam and produces a total score. Subjects were independently administered the AMSE and the Autism Diagnostic Observation Schedule (ADOS). The ADOS was used to estimate the most effective criterion cut-off on the AMSE. A score of five or greater produced excellent sensitivity and good specificity in a high-risk sample. Internal consistency was acceptable and inter-rater reliability was good to excellent. Preliminary findings indicate excellent classification accuracy and suggest that the AMSE provides a rapid and reliable observational assessment in a high-risk population.