The restorative potential of isogeneic and fully allogeneic thymic implants to restore in vivo antibody responsiveness to a thymus-dependent antigen has been examined in thymectomized clawed toads. Isogeneic clones (Xenopus laevis/gilli and X. laevis/muelleri hybrids) of known major histocompatability complex (MHC) haplotypes were thymectomized at 5-7 days, implanted with MHC-identical or -mismatched (normal or irradiated ) thymuses from 5-week-old larvae and 4 months later injected with dinitrophenylated keyhole limpet hemocyanin. IgM antibody responsiveness (measured by phage inactivation) was restored in terms of its quantity, affinity and specificity in those thymectomized animals given two haplotype-different thymuses. Isoelectric focusing data revealed that low molecular weight antibody production was also restored with isogeneic and allogeneic thymus and that the antibody spectrotypes were of the host type. The finding that in vivo T-B collaboration in thymectomized animals develops normally following thymus implantation, even when the thymus genotype is disparate from the host, is discussed both in the light of previous experiments revealing MHC restriction of Xenopus T helper cells in vitro and in terms of the role of the thymus in promoting adaptive differentiation of this lymphocyte subset.