Central dopaminergic activity has been assumed to play a role in the efficacy of stimulant drugs in attention deficit/hyperactivity disorder (ADHD), although supporting evidence has been scant. This study examined baseline cerebrospinal fluid (CSF) of boys with ADHD in relation to response to three different stimulant drugs. Forty five boys with DSM-III-R-diagnosed ADHD had a lumbar puncture before double-blind trials of methylphenidate, dextroamphetamine, and placebo. Sixteen also received pemoline as part of a subsequent open trial. Stepwise linear regressions determined significant predictors of drug response. Our prior report of a positive significant correlation between CSF homovanillic acid (HVA) and ratings of hyperactivity on placebo was replicated in a new sample of 20 boys. After baseline symptom severity, CSF HVA was the best predictor of stimulant drug response, with significant independent contribution to four of the ten measures of hyperactivity that changed significantly with medication. Higher HVA predicted better drug response, and lower HVA was associated with worsening on some measures. This supports the mediating role of central dopaminergic activity in stimulant drug efficacy in childhood hyperactivity.