A method has been described for the study of the central effects produced by the intracerebral injection of drugs in the unanaesthetized mouse. The effects observed were in good agreement with those obtained after similar injections in cats, dogs and human beings. After intracerebral injection, drugs of diverse structure produced certain generalized effects: changes in positioning of the tail, stupor, hyperexcitability and tachypnoea. Both acetylcholine and methacholine produced an akinetic seizure and depression, but the latter compound also caused lacrimation and salivation. Atropine produced piloerection, increased sensitivity to sound and touch, clonic convulsions and scratching, whereas hexamethonium caused Parkinsonian-like muscle tremors and peripheral vasodilatation. After adrenaline, hyperexcitability, exophthalmos, stupor and death from pulmonary oedema were observed, but (+)-methylamphetamine produced only piloerection and exaggerated activity in response to sound and touch. Ergotamine caused a decreased sensitivity to sound and touch, micturition, and stupor, while ergometrine caused clonic convulsions, piloerection, defaecation and stupor.