The intolerance of children with autistic disorder to changes in their routine or environment is well known, typically presenting with acute symptoms of anxiety, panic, irritability, or agitation. In a clinical sample of children (6-12 years old) with autistic disorder and transition-induced behavioral deterioration, 8 of 9 patients showed a clinically significant improvement in response to sertraline treatment. Only one child was taking concurrent psychotropic medication. Therapeutic doses were surprisingly low in all cases (25-50 mg daily), with a clinical response appearing generally in 2-8 weeks. Adverse effects were minimal (one child developed stomachaches), except for apparent sertraline-induced behavioral worsening in 2 children when their doses were raised to 75 mg daily. In 3 children, an initial satisfactory clinical response appeared to diminish after 3-7 months of treatment, despite steady or increased doses. In 6 patients, the beneficial effects persisted throughout the several-month follow-up period. Only four of the children's families were identified as having mood and/or anxiety disorders. This open-label study suggests that short-term sertraline treatment may reduce the behavioral reactions seen in association with situational transitions or environmental changes in children with autistic disorder, though the beneficial effect may be only temporary in some children. Our experience suggests that small doses of sertraline may be effective and that some children may require divided doses of sertraline during the day. Controlled studies are needed to determine the efficacy, safety, and pharmacokinetics of sertraline in treating this "need for sameness," both in short-term and long-term studies of children with autistic disorder.