Antigen stimulation in mice such as occurs with the rejection of an allogeneic tumor graft caused a substantial rise in serum glycolipid Ia levels. However, mice bearing a measurable syngeneic tumor had no detectable Ia antigens in their sera; this observation was made in several different strains of inbred mice with 5 different tumors. In each instance the serum Ia level fell as the tumor grew progressively, reached zero at about the time the tumor was visible, and remained at this zero level until the mouse died. Similar results were found in humans: Tumor-bearing patients had markedly suppressed serum Ia levels. The mechanism of the fall in serum Ia glycolipid levels is not known, but the measurement of the serum Ia glycolipid content appears to reflect the level of activation of the immune system, and the suppression of serum glycolipid Ia levels found in tumor-bearing mice and patients may have important clinical implications.