We report the existence of a protein in normal human urine that binds, specifically and with high affinity (Kd∼ 1.9 nM) to human interleukin 4 (IL-4) and thereby prevents the binding of the cytokine to the high affinity receptor. The urinary binding protein has a molecular weight of 40 kD and 23 kD after deglycosylation. The binding protein has been purified by affinity chromatography. It inhibited IL-4-dependent (but not IL-2-dependent) T-cell proliferation. This protein may play a role in vivo in regulating the biological activities of this important immunoregulatory cytokine.