Immunomodulation with Cyclosporin may allow better management of the patient with insulin dependent diabetes mellitus. The cellular effects of CsA were determined on rabbit lymphocytes which are a resting (Go) population for which the kinetics of activation have been defined. Cyclosporin inhibited polyclonal T-cell activation as well as B-cell activation by T-dependent and T-independent antigens. Resting lymphocytes were the exclusive target of CsA. Primed or activated cells, as well as cells in G1, were resistant to the drug. Cyclosporin inhibited the generation of T-helper cells and spared suppressor cell generation. The inhibitory effects of cyclosporin were not reversible.