Cyclosporin A (CyA) is a new immunosuppressive drug of very considerable and widespread interest not only for clinicians and transplant immunologists but also for cell biologists concerned with activation mechanisms, as it causes a selective blockade of lymphocyte proliferation. Clearly, the molecular biology of CyA action is of fundamental importance, and in attempting to understand this we have looked for a cell surface receptor. We used indirect staining with antibody (at 4 degrees C and in azide) to ensure that only those CyA molecules held at the cell surface would be seen. The drug molecules which partition into the cell membrane, due to the extreme lipophilicity of CyA, are not detected by extracellular antibody. This technique differs from other methods using a directly labelled drug, where it is not possible to discriminate between specific and non-specific binding. Using high sensitivity flow cytometric analysis we were unable to find CyA on resting lymphocytes, whereas lymphocytes activated by concanavalin A (Con A) or mixed lymphocyte reaction (MLR) showed a CyA-dependent increase in fluorescence.