Vaccinia virus gene B15R is shown to encode an abundant, secretory glycoproteln that functions as a soluble interleukln-1 (IL-l) receptor. This IL-1 receptor has novel specificity since, in contrast with cellular counterparts, it binds only IL-1 fl and not IL-la or the natural competitor IL-1 receptor antagonist. The vaccinia IL-1 p receptor is secreted when expressed in a baculovirua system and competitively inhiblted binding of IL-1 p to the natural receptor on T cells. Deletion of B15R from vaccinla virus accelerated the appearance of symptom8 of illness and mortality In intranasally infected mice, auggeMing that the blockade of IL-lg by vaccinia virus can diminish the systemic acute phase response to infection and modulate the severity of the disease. The IL-10 binding activity is present in other orthopoxvirusea.