Manganese oxides with a perovskite structure’ exhibit a transition between a paramagnetic insulating phase and a ferromagnetic metal phase. Associated with this transition is an effect known as colossal magnetoresistance(2-5) (CMR)-in the vicinity of the transition temperature, the materials exhibit a large change in resistance in response to an applied magnetic field. Such an effect, if optimized, might find potential application in magnetic devices. But the criteria for achieving (and hence optimizing) CMR are not clear, presenting a challenge for materials scientists, The accepted description of CMR in the manganite perovskites invokes the ’double-exchange’ mechanism, whereby charge transport is enhanced by the magnetic alignment of neighbouring Mn ions of different valence configuration (Mn3+ and Mn4+), and inhibited by the formation of charge-induced localized lattice distortions(6,7) Here we report the existence of a large magnetoresistive effect in a class of materials-Cr-based chalcogenide spinels-that do not possess heterovalency, distortion-inducing ions, manganese, oxygen or a perovskite structure. The realization of CMR in compounds having a spinel structure should open up a vast range of materials for the further exploration and exploitation of this effect.