If the clinical symptoms of mania are a consequence of increased activity in central dopaminergic (DA) pathways in predisposed individuals, then drugs increasing DA neurotransmission should precipitate or exacerbate mania in such people, whereas drugs which reduce DA neurotransmission should ameliorate manic symptoms. Of the drugs which enhance DA neurotransmission, those which increase synthesis of DA (levodopa), those which promote DA release (amphetamine), and those which act directly as agonists or DA receptors (bromocriptine) have all been shown to precipitate mania. Conversely, drugs which reduce DA neurotransmission by inhibiting synthesis (alpha-methylparatyrosine) or by blocking DA receptors (pimozide) are effective in reducing manic symptoms. DA systems are not working in isolation; evidence is presented showing an influence on manic illness of central cholinergic and GABA-ergic processes. It is suggested that there is an interacting set of neurotransmitter pathways linking the limbic system and the ventral tegmental (A10) area involving DA, acetylcholine and GABA upon which drugs can act to influence the course of a manic illness.