1 Noradrenaline caused a small contraction of the cat isolated spleen strip bathed in a calcium-free solution; this contraction was greatly potentiated by cocaine. This potentiation was also present in isolated spleen strips where noradrenaline stores were depleted by reserpine. The maximum response of the spleen strip to noradrenaline in the absence of extracellular calcium was also increased by cocaine. 2 The disodium salt of ethylenediaminetetraacetic acid (Na-EDTA) but not Ca-EDTA antagonized the potentiation of the response to noradrenaline by cocaine in a calcium-free solution, and greatly reduced the magnitude of subsequent responses to noradrenaline and cocaine. 3 Strontium caused equivalent contractions of normal and reserpine-treated spleen strips bathed in a calcium-free solution. These responses were potentiated by cocaine. 4 Histamine caused a small contraction of the isolated spleen strip bathed in a Ca-free solution. Cocaine failed to potentiate these very small histamine contractions, but did potentiate the contraction of these same strips in response to noradrenaline. 5 It is concluded that the potentiation of the response of the isolated spleen strip to noradrenaline by cocaine in the absence of extracellular calcium is due to a mechanism other than decreased neuronal uptake of noradrenaline. It is suggested that cocaine makes a bound store of calcium more available to promote contraction of the spleen strip by noradrenaline.