Part 1 of this study attempted to discriminate clinical responders and nonresponders to methylphenidate (MPH) on the basis of neuropsychological deficit profiles. Part 2 addressed the question to what extent MPH might ameliorate these deficits. Hyperactive clinical responders (n = 30) and nonresponders (n = 28) to MPH, were compared to normal controls (n = 27) on selective and sustained attention tasks and on conventional psychological and neurological measures. The responders took part in a randomized double-blind placebo-controlled crossover study. They ingested a placebo (PL) or MPH (0.3-0.6 mg/kg/day) during 4 weeks, and were then tested. After crossover, another period of 4 weeks was concluded by a second test series. Compared to controls, both responders and nonresponders showed attention deficits in encoding, memory search, and decision operations, as well as in focused and sustained attention, vigilance, and use of feedback. These deficits were the most severe in the responders. Anamnestic data, IQ scores, and neurological variables did not discriminate between groups. MPH selectively alleviates attention deficits. MPH did not affect divided attention, except for an increased accuracy of response organization. The drug, however, greatly improved focused and sustained attention, vigilance, impulsivity, and the behavioral adaptivity to feedback.