In the chicken, the B cells develop in a specialized organ, the bursa of Fabricius. Earlier it was shown that neonatal bursal cells treated with polyclonal anti-chicken immunoglobulin antibodies are not able to recolonize the bursa when transferred into cyclophosphamide-treated chicks. In this study, 4-day-old bursal cells were treated with different polyclonal and monoclonal anti-immunoglobulin antibodies and transferred into 4-day-old cyclophosphamide-treated chickens. Two monoclonal anti-chicken IgM antibodies, CVI-59.7 and 21-2B2, recognizing distinct epitopes of the mu heavy chain, were inhibitory. Incubation of cells with 21-2B2 antibody caused about 90% inhibition of bursal recolonization. After incubation with CVI-59.7 antibody the inhibition was 50%. The high inhibition by 21-2B2 antibody was also seen when F(ab')2 fragments of the antibody were used. These results suggest that the entry of the cells needed for bursal recolonization is inhibited almost totally by 21-2B2 antibody, or that this antibody blocks further proliferation of the cells in bursal follicles. In conclusion, we have shown that a mu heavy chain epitope is intimately involved in the recolonization of bursal follicles, and distinct epitopes of the mu heavy chain are not equally important in this process.