The effects of pretreatments of BALB/c mice with several conjugates of MDP and MDP-Lys to ovalbumin before immunization with ovalbumin (OA) were tested on the anti-OA IgE responses. Pretreatment with MDP-Lys-OA, but not with MDP-OA, induced an inhibition of the anti-OA primary and secondary responses, as measured by passive cutaneous anaphylaxis (PCA) and also by mast cell degranulation. The inhibition by pretreatment with MDP-Lys-OA was obtained whether it was administered in Freund's incomplete adjuvant (FIA) or in saline. This IgE suppression was accompanied by an enhancement of IgG2a and IgG2b anti-OA antibodies, with no change in the specific IgG1 levels. Loss of antigenicity of OA, detected by the lack of degranulation of peritoneal mast cells sensitized by IgE anti-OA, was observed in the MDP-Lys-OA but not in the MDP-OA conjugates. This loss of antigenicity appears to correlate with the ability of the conjugate to induce suppression of the specific IgE response.