The effects of the antiglucocorticoid RU486 on the expression of low and high affinity interleukin-2 receptors (IL-2R) in phytohaemagglutinin (PHA)-activated human peripheral blood lymphocytes were investigated. We demonstrated that RU486 inhibits in a dose-dependent way the expression of both classes of IL-2R, thereby mimicking the effects of the glucocorticoid agonist dexamethasone. The maximal effect on the low affinity binding sites was observed at 10 μM (28 ± 2% of control, P < 0.001) and on the high affinity IL-2R at 1 μM (from2938 ± 74 to 437 ± 108 binding sites per cell, P < 0.001). This inhibition of IL-2R expression occurs at a pretranslational level since RU486 decreased the accumulation of β-chain IL-2R mRNA transcripts. Our data support the concept that the antiglucocorticoid RU486 at pharmacological concentrations can exert agonistic-immunosuppresive effects.