This study compares the behavioral and cardiovascular response to methylphenidate (0.5 mg i.v.) in 10 cocaine abusers and 20 controls. Methylphenidate induced a long-lasting increase in blood pressure and pulse rate in both groups of subjects. It also induced a short-lasting ‘high’ (27 min) and longer-lasting ‘restlessness’ (67 min). In the normal subjects, but not in the cocaine abusers, methylphenidate significantly increased sexual desire and induced a subjective experience of ‘loss of control’. In the cocaine abusers, methylphenidate consistently induced cocaine craving. While 90% of the cocaine abusers reported methylphenidate as pleasurable, only 50% of the normal subjects did. Cocaine abusers reported that the ‘high’ induced by methylphenidate was similar to that of cocaine but lasted longer and was associated with more physical effects.