Peripheral blood mononuclear cells from ragweed-sensitive individuals formed soluble factors that inhibited rosette formation of Fc epsilon receptor (+) cells with IgE-coated ox erythrocytes when the cells were incubated with ragweed antigen E and human IgE. Either antigen E alone or IgE alone failed to induce the formation of the rosette inhibiting factors. Two-way mixed lymphocyte culture from 2 normal individuals followed by incubation of the activated lymphocytes with IgE induced the formation of the rosette-inhibiting factor. Normal human mononuclear cells cultured in the presence of T cell growth factor (TCGF) formed the soluble factor when they were incubated with IgE. The rosette-inhibiting factor in culture filtrates was specifically absorbed with IgE-coupled Sepharose and was recovered from the beads by elution at acid pH, indicating that the soluble factors have affinity for IgE. Because the lymphocytes cultured with TCGF were mostly T cells and contained neither B cells nor monocytes, it appears that the IgE-binding factors are derived from T cells.