In the last few years many authoritative reviews have appeared on antibiotics that translocate ions across membranes ( 1-8). It is unfortunate, in our opinion, that biologists who could utilize these antibiotics in their experimental studies may be dissuaded from reading these comprehensive reviews because of their mathematical content. The purpose of our review, therefore, is to summarize briefly the currently accepted paradigm (9) of how the antibiotics function at a molecular level and to illustrate their use with selected examples from the biological literature. The anti biotics discussed here all facilitate the passive movement of ions across membranes, and the available data suggest that this is the basis for their biological activity. Knowledge gained from the study of these antibiotics may be applied in at least three different ways to the investigation of biological phenomena. First, the interaction of these antibiotics with artificial lipid membranes may be studied as a model for the permeation of ions through biological membranes. Alamethicin, for instance, induces a voltage-dependent conductance in lipid membranes ( 10-12) that may be considered a model for the endogenous voltage-gateable channels in nerve membranes (13-15). Nystatin also forms pores in bilayers ( 16) and these can serve as models for the putative pores in erythrocytes ( 17). Second, certain antibiotics can serve as useful probes of both membrane structure and function. The use of filipin as a fluorescent probe for the presence and localization of cholesterol and related sterols in biological membranes (18) and the use of nonactin as a probe of surface potentials ( 19, 20) illustrate this application. Third, the antibiotics can be used to perturb biological membranes and the gradients of concentration and potential that exist across them. Valinomycin, for example, has been used to increase the K + permeability of erythrocytes and thereby demonstrate that the high chloride permeability is due mainly to exchangc diffusion (21 ). Calcium ions have been postulated to be involved in the control of many physiological processes: the release of neurotrans-