We examined whether grief and general distress reactions characterized mothers' reactions to their child's ASD diagnosis, and whether these two types of reactions had unique predictors. Hierarchical regression analyses were conducted on data collected from 362 mothers recruited from the Interactive Autism Network (IAN). The mothers were predominantly white, highly educated, and married. Grief reactions were positively associated with perceiving ASD as a loss and as unjust. Distress was positively associated with previous mental health issues, mothers' reports of their child's aggressive behavior, identity ambiguity, and less social support. Internal attributions were positively related to grief and distress. Discussion focuses on why the distinction between these two types of affective reactions may be useful for parents and professionals.