Background: Children with autistic spectrum disorder (ASD) have difficulties understanding and using nonverbal communication. Handshaking is an expressive gesture that requires adequate skills for social interaction and, because of its highly emotional characteristic for patients with ASD, may reflect their ability for social responsiveness. Unlike eye contact or complex social behavior, this gesture has not been studied in the past. We developed a rating scale intended to evaluate social responsiveness through handshaking, in patients with ASD. Method: A group of patients with ASD (n = 20), aged 9 to 18 years, was compared with 2 age-matched groups, one of patients with attention deficit/hyperactivity disorder (n = 20) and the other is of patients with mild (IQ, 55-70) mental retardation (n = 20). To rate the handshaking behavior, we designed a Handshaking Assessment Scale (HAS) that includes 8 Yes/No items. The predefined cutoff point was a minimum of 4 Yes answers. Results: Significantly more patients with ASD (13/20) had abnormal HAS (Yes answers, ≥4) than either in the attention deficit/hyperactivity disorder group (1/20; P <.0001) or in the mental retardation group (5/20; P <.025). Conclusion: There seems to be a strong association between poor handshaking skills and autistic psychopathology, as compared with the 2 control groups. As was demonstrated by the brief and easy-to-administer HAS assessment tool, it may be advisable to use handshaking more widely as a diagnostic procedure for ASD or include it in larger diagnostic batteries. Large-scale studies are needed to substantiate our observation.