The specificities of antibodies of different Ig classes against trimellityl (TM)-human serum albumin were examined by a radioimmunoassay inhibition technique. The antisera were from workers exposed to trimellitic anhydride who had 4 differing respiratory diseases. The studies demonstrated similarities between reactivities of antibodies of different Ig classes in these workers in that inhibition of antibody to TM-HSA required markedly less TM-HSA on a molar basis than TM-ovalbumin (OA) or sodium trimellitate (NaTM), the hapten for the trimellityl group. The results appears best explained by formation of new antigenic determinants on altered HSA molecules with the TM group forming a component of some of the new antigenic determinants. NaTM in high concentration could not completely inhibit the IgG antibodies of 2 sera suggesting either very low affinity for the hapten or that some of the antibodies might possibly be directed against new antigenic determinants formed from the reaction of TMA with HSA but that the TM group might not be a part of the antigenic specificity. The results of some studies also suggested that there were similar antigenic specificities on TM-HSA and TM-OA but of lesser concentration or lower affinity on the latter molecules. Passive transfer studies using a serum containing IgE antibodies against TM-HSA demonstrated that these human IgE antibodies will passively sensitize rhesus monkey skin. Neutralization of the cutaneous IgE antibodies occurred with TM-HSA but not with a great molar excess of NaTM in analogy with the in vitro studies.