The present study reports preliminary data from two unselected samples of carefully diagnosed autistic subjects (children and adults) and an assessment procedure that includes a large sample of items, appropriate for lower-functioning autistic subjects, with multiple presentations within and between sessions 1 week apart. The study seeks to determine (1) whether a raised incidence of non-right-handedness exists in these samples (2) if so, what constructs best represent this shift in the handedness distribution (i.e., phenotype and CNS substrate) and (3) whether these handedness phenotypes are associated with different levels of cognitive functioning. The results reveal a dramatic shift away from right-handedness in both autistic samples, due to a raised incidence of two phenotypes, manifest left-handedness and ambiguous handedness. The ambiguously handed, who were postulated to represent substantial bilateral CNS pathology due to early brain injury, were found to have much lower intellectual scores in one of the study samples.