Background: The Social Responsiveness Scale (SRS) is a parent-completed screening questionnaire often used to measure autism spectrum disorders (ASD) severity. Although child characteristics are known to influence scores from other ASD-symptom measures, as well as parent-questionnaires more broadly, there has been limited consideration of how non-ASD-specific factors may affect interpretation of SRS scores. Previous studies have explored effects of behavior problems on SRS specificity, but have not addressed influences on the use of the SRS as a quantitative measure of ASD-symptoms. Method: Raw scores (SRS-Raw) from parent-completed SRS were analyzed for 2,368 probands with ASD and 1,913 unaffected siblings. Regression analyses were used to assess associations between SRS scores and demographic, language, cognitive, and behavior measures. Results: For probands, higher SRS-Raw were associated with greater non-ASD behavior problems, higher age, and more impaired language and cognitive skills, as well as scores from other parent report measures of social development and ASD-symptoms. For unaffected siblings, having more behavior problems predicted higher SRS-Raw; male gender, younger age, and poorer adaptive social and expressive communication skills also showed small, but significant effects. Conclusions: When using the SRS as a quantitative phenotype measure, the influence of behavior problems, age, and expressive language or cognitive level on scores must be considered. If effects of non-ASD specific factors are not addressed, SRS scores are more appropriately interpreted as indicating general levels of impairment, than as severity of ASD-specific symptoms or social impairment. Additional research is needed to consider how these factors influence the SRS' sensitivity and specificity in large, clinical samples including individuals with disorders other than ASD. (Contains 3 tables and 1 figure.)