Autism is a complex developmental disorder characterized by deficits in social communication and interaction as well as the presence of restricted and repetitive behaviors. Autism occurs about four times more frequently in males than in females, and the male-to-female ratio can be as high as 10:1 among high-functioning individuals. Previous studies suggest that females who have autism may show weaker language and motor skills, greater social impairment, and fewer restricted and repetitive behaviors compared with males who have autism. However, most studies of sex differences in behavioral symptoms and cognitive characteristics have included only small numbers of females, making conclusions tentative. Thomas Frazier and his colleagues at the Cleveland Clinic Foundation are seeking to better understand sex differences in autism using the Simons Simplex Collection, which includes data from more than 2,000 males and 350 females with autism. The researchers plan to evaluate sex differences in social communication and restricted and repetitive symptoms, other psychiatric symptoms, verbal and visual ability, specific language skills and adaptive daily living skills. Sex discrepancies in the prevalence of autism also suggest a possible need for sex-specific thresholds when making the diagnosis. Frazier’s team plans to use autism symptom and trait information from unaffected first-degree relatives to examine whether families with affected females have a greater ‘genetic load,’ meaning that females require more genetic ‘hits’ to cross the threshold from neurotypical behavior to autism. If unaffected first-degree relatives from female-affected families show higher autism trait levels than do unaffected relatives from male-affected families, this idea would be supported. Finally, with the newly proposed DSM-5 diagnostic criteria in mind, the researchers aim to evaluate whether males and females should be assessed for autism by different criteria that are based on sex-specific symptom patterns.