Tests of mediation in treatment trials can illuminate processes of change and suggest causal influences in development. We conducted a mediation analysis of a previously published randomised controlled trial of parent-mediated communication-focused treatment for autism against ordinary care, with 28 children aged 2–5 years (Aldred et al. in J Child Psychol Psychiatr 45:1–11, 2004 ). The hypothesised mediating process, targeted by the intervention, was an increase in parental synchronous response within parent–child interaction. The results showed partial mediation, with change in synchrony accounting for 34% of the positive intervention effect on autism symptomatology (Autism Diagnostic Observation Schedule communication and social domain algorithm); the result was confirmed by bootstrap estimation. Improved parental synchronous response to child communication can alter short-term autism symptom outcome with targeted therapy.