The Autism Observation Scale for Infants (AOSI) was developed to detect and monitor early signs of autism as they emerge in high-risk infants (all with an older sibling with an autistic spectrum disorder). Here we describe the scale and its development, and provide preliminary data on its reliability. Inter-rater reliability both for total scores and total number of endorsed items is good to excellent at 6, 12 and 18 months; reliability is more modest for individual items, particularly in 6-month-olds. Test-retest reliability of the AOSI at 12 months of age is within acceptable limits. Evidence that the AOSI provides reliable data is the first critical step towards evaluating its efficacy in distinguishing high-risk infants who develop ASD.