The half-lives of two classes of rat immunoglobulins with homocytotropic properties, i.e., IgE and IgG2a, in the circulating blood and in the skin were studied. The catabolism of both normal (reaginic) and pathological (myeloma) IgE proteins in circulation was found to be extremely rapid with a half-life of 12 h. In contrast, the half-life of IgE antibody in the homologous skin was calculated to be 7.4 days. On the other hand, the half-life of IgG2a in circulation was about 5 days regardless of normal or pathological origin. IgG2a protein was, however, rapidly cleared from the injected skin site with a half life of 2.4 days, a value not longer than that obtained with nonskin-sensitizing goat IgG. The results indicate that rat IgE has an extremely short half-life in circulation despite of its sensitization period in tissues, and that the affinity for the target cells, as well as the mode of sensitization, of the two classes of homocytotropic antibodies, IgE and IgG2a, is different.