Platelet-activating factor (PAF) is, at physiological (nanomolar) concentrations, a potent mediator of inflammation and coagulation. At pharmacological (micromolar) concentrations, PAF induces a variety of effects in diverse tissues. Here we show that PAF at micromolar concentrations is a membrane perturbant. Micromolar PAF alters the properties of channels formed by gramicidin A, and at concentrations greater than or equal to 4 microM disrupts the barrier properties of the host lipid bilayer. PAF thus can act as a detergent and non-specifically alter the behavior of membranes and membrane proteins. This may provide an explanation for some of the effects of PAF seen at high concentrations in vitro.