Native high molecular weight dextran induces a thymus-independent response in BALB/c mice. When the dextran epitope is linked to a protein carrier the response becomes thymus-dependent. IgG antibodies produced after secondary immunization had epitope specificity and idiotope of myeloma M104E. The antibody of M104E (μ,λ1) is representative for antibodies produced by mice with immunoglobulin haplotype Igh a in response to immunization with dextran B1355S. Myeloma product and physiological antibodies share specificity for the α(1–3) glucosidic linkage and have idiotopes in common. Mice with haplotypes other than Igh a (e.g. Igh b) are unable to yield this type of response. A complete rearranged immunoglobulin μ-chain gene with a VDJ-region from BALB/c (Igh a) myeloma protein M104E had been introduced into the genome of BALB/c congenic mice having the haplotype Igh b. As was shown previously in our laboratory the M104E p-chain transgene confers Igh a-type reactivity to Igh b Mice. In experiments described in this report we used the thymus-dependent form of the antigen to immunize mice bearing the M104E λ 1-chain, either alone or together with the λ 1-chain, as a transgene on an Igh b genetic background. Serological analysis revealed a class switch to IgG very similar to that seen in BALB/c mice with respect to magnitude, kinetics, epitope and idiotope specificity. The pattern of IgG subclass expression was indistinguishable in p-chain transgenic Igh b and normal BALB/c mice. The class switch occurred even though, as is shown here, the transgene had become incorporated in a site not linked to the Igh locus on chromosome 12. We propose a model for this apparent trans-chromosomal class switch recombination which is based on mechanisms known for conventional switch recombination.