The present experiment was an attempt to clarify the pharmacological properties of oxatomide. Oxatomide administered i.v. was found to be as active as disodium cromoglycate (DSCG) in inhibiting the IgE-mediated 48 hr homologous PCA in rats. In contrast to DSCG, oxatomide was also effective when administered p.o. Oxatomide inhibited the IgG-mediated 4 hr heterologous PCA in guinea pigs. However, DSCG did not prevent this reaction. In an attempt to determine at what stage in the PCA reaction oxatomide was effective, the experiment was performed utilizing a double sensitization technique with two different IgE antibodies, anti-dinitrophenylated-ascaris extract and anti-egg albumin. When the same antigen was challenged twice in sequence, the second antigen challenge did not produce the PCA regardless of the presence or absence of oxatomide at the initial antigen challenge. However, the presence of oxatomide during the period of the first challenge preserved completely the PCA responsiveness of the tissue to the second challenge with the other antigen. Similar results were obtained with DSCG. These results suggest that oxatomide may not impair the antigen-antibody combination, but it probably prevents the release of chemical mediators in a manner similar to DSCG.