New pharmacotherapies for intravenous abuse of opioids and stimulants are needed to control the spread of acquired immunodeficiency syndrome. To facilitate development of these new medications, it is useful to review the neurobiology of these abused drugs from the perspectives of neurotransmitter receptors and synaptic mechanisms in the brain. For the opioid drugs, the roles of the endogenous opioid system and the cyclic adenosine monophosphate second messenger system are reviewed. For the stimulants, the dopaminergic and noradrenergic systems are examined as the basis for reinforcement and withdrawal from chronic stimulant abuse, while the important role of serotonin systems for the stimulant-derived "designer drugs" such as 3,4-methylenedioxymethamphetamine or "ecstasy" is indicated.