Abstract A method is described for identifying Ca ++ ionophores using the protozoa Actinosphaerium. This organism is a free-floating spherical form with filamentous axopods radiating from the surface. The axopods are composed of microtubules that disaggregate upon exposure to intracellular Ca ++. In the presence of an appropriate ionoprfore, extracellular Ca ++ will pass the cell membrane, enter the cell, and disrupt microtubules. The resultant shortening of axopods can be easily quantified under a microscope. This system may prove to be a valuable research tool in the identification of compounds that possess the ability to facilitate transmembrane Ca ++ movement.