The immunogenic D-amino acid synthetic polypeptide, 247, p(D-Tyr, D-Glu, D-Ala), was shown to induce specific immunological paralysis in small doses in mice. The corresponding L-amino acid polypeptide, 253, p(L-Tyr, L-Glu, L-Ala) primes mice in similar doses. The metabolism and fate of these polymers were studied and correlated with their immunological activity in mice. Using 125I as label, it was found that the D-polymer is broken down twenty-two times more slowly than the L-polymer; in addition some of the D-polymer appeared to be excreted intact in the urine. After footpad injection, 200–1000 times as much D-polymer as L-polymer was retained in draining lymph nodes and spleen. Much of the D-polymer is retained in the kidney, liver and injection site; the D-polymer in the kidney is localized in proximal convoluted tubule cells. Autoradiographs of sections of draining lymph nodes show the D-polymer localized almost exclusively in macrophages, while the L-polymer was found initially in macrophages and increasingly also in germinal centres, its presence in the latter being correlated with the appearance of circulating antibody.