Volunteer addicts were administered iv loading doses of cocaine, followed by 4-hr cocaine infusions that maintained steady-state conditions. The loading doses were followed by the "rush" and "high" subjective effects that users typically experience; cocaine infusions maintained the experience of drug "high", but not "rush". In a subsequent experiment, haloperidol pretreatment did not alter cocaine "rush" but partially attenuated cocaine "high." During cocaine infusions, we also noted suspicious and paranoid behavior, which were blindly rated by nurses. During one of the infusion conditions, the degree of suspiciousness observed was related to the amount of cocaine previously administered. Although cardiovascular responses to cocaine were marked, we found no alterations in plasma catecholamines following cocaine administrations. Baseline homovanillic acid (HVA) levels, however, were related to the degree of suspiciousness observed following cocaine dosing. The potential contributions of dopaminergic systems and physiological sensitization to the development of the psychiatric toxicity of cocaine are discussed.