Acute toxicity of desipramine in mice was shown to be influenced by other drugs. Pretreatment with reserpine but not with chlorpromazine, disulfiram, or p-chlorophenylalanine protected mice against desipramine toxicity. Reserpine protection was reversed by dopa or dopa and disulfiram but not by methyldopa or 5-hydroxytryptophan. These results suggested a relationship between catecholamines and desipramine toxicity.