Objective: The purpose of this study was to examine the efficacy of psychostimulant medication in a naturalistic sample of preschoolers. Benefits and side effects for methylphenidate and mixed amphetamine salts (Adderall) were examined. Method: Twenty-eight preschoolers (ages 4.0-5.9) participated in the present investigation. They were obtained consecutively from a large sample of suburban children assessed for attention-deficit/hyperactivity disorder. After having received various dosing levels of a stimulant in a placebo-controlled crossover design, best dose was assigned based on the lowest Abbreviated Symptoms Questionnaire T score received in a given week. All analyses compared best dose ratings to placebo ratings. Results: Preschoolers' behavioral ratings by parents and teachers were improved as a function of stimulant medication. More than 82% of the medicated sample improved their behavioral rating by at least 1 SD as demonstrated by receiver operating characteristic (ROC) analyses, with more than 50% of medicated preschoolers improving by more than 2 SD. Side effects were infrequent at best dose of medication. Conclusions: Clinically significant changes in behavioral ratings of preschoolers were noted in response to stimulant medication. Both stimulants were well tolerated. ROC curves were useful for clearly depicting on a case-by-case basis how much improvement was derived from psychopharmacological treatment.