A 5-week open trial of venlafaxine was conducted in 16 children and adolescents (mean age 11.6 years) with attention-deficit/hyperactivity disorder (ADHD) in order to estimate the appropriate dosage range and to determine the extent of side effects. Subjects were evaluated using a structured clinical interview and a computerized diagnostic assessment, and subjects diagnosed with ADHD and without comorbid depression were asked to enter the study. Conners Parent Rating Scale (CPRS) and Conners Continuous Performance Test (CPT) were performed at baseline and at the end of the 5-week trial. Two subjects were lost to follow-up. Of the remaining 14 patients, 7 subjects displayed a decrease of at least one standard deviation from their baseline on one of the CPRS subscale scores and had subjective reports from parents of improved behavior. There were no statistically significant effects of venlafaxine on reaction times or on the number of commission and omission errors on CPT. Three ADHD subjects displayed a worsening of their hyperactivity and required discontinuation of venlafaxine, and nausea led to drug discontinuation in 1 patient. The mean daily dose of venlafaxine was 60 mg (1.4 mg/kg), administered 2-3 divided doses, there were no effects on blood pressure or heart rate. In this sample, low doses of venlafaxine appeared to be effective in reducing behavioral but not cognitive symptoms of ADHD in 7 of 16 children and adolescents (44%), and adverse effects were not tolerable in 4 of 16 patients (25%). These preliminary results suggest that venlafaxine may aggravate symptoms of hyperactivity, consistent with the behavioral activation reported with fluoxetine and sertraline in children.