The effects of lithium on spontaneous activity, exploratory activity, hyperactivity and stereotypy induced by drugs, drug-induced hypoactivity and activity rhythms of animals are reviewed. Attention is given to the rationale for the studies and the relation of research on motor activity of animals to the therapeutic and prophylactic actions of lithium against manic-depressive illness. The most consistent effects of lithium on motor activity of animals are found on exploratory activity, hyperactivity and stereotypy induced by drugs that alter monoaminergic neurotransmission, and rhythmic activity driven by endogenous biological clocks. Suppressant effects of lithium on motor activity appear related to alterations in monoaminergic and cholinergic neurotransmission, to actions of thyroid hormones and to alterations in postsynaptic depolarization. Potentiating effects of lithium on activity seem to be due to alterations in the sensitivity of monoamine receptors. Some suggestions are made concerning further studies of interest to investigate the mechanisms of action of lithium on motor activity.