Several reports demonstrate that interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta), although distantly related at the primary sequence level, bind to the same receptor. This raises the question of what separation, if any, there might be between their biologic activities. Receptor binding assays and cross-competition studies in three Epstein Barr virus (EBV) positive cell lines showed that a subset of IL-1 receptors may bind IL-1 alpha preferentially and that a separate subset may bind IL-1 beta preferentially. Crosslinking studies with 125I-IL-1 alpha or 125I-IL-1 beta demonstrated the expression of both relative molecular mass (Mr) 80,500 IL-1 receptor, known to be T cell-specific, and Mr 69,500 IL-1 receptor, recently detected on B-cell lineage only. Whether the high affinity binding sites correspond to Mr 80,500 and the low affinity binding sites to Mr 69,500 remains to be elucidated.