In vivo studies of lymphocyte biology have used intravenous (i.v.) injection as the primary mode of cell transfer, a protocol consistent with the anatomic distribution of most lymphocytes. However, for study of peritoneal cavity B cells, i.v. injection does not correlate with anatomical localization. This report describes the restoration of B‐cell function in B lymphocyte‐defective X‐chromosome‐linked immune‐defective (XID) mice after intraperitoneal transfer of immunoglobulin heavy chain (Igh)‐disparate peritoneal cavity (PerC) cells. In contrast to i.v. transfer, intraperitoneal (i.p.) transfer restored B‐cell function in young, but not adult (>8 weeks), XID mice. When host and donor Igh allotype matched, PerC B‐cell engraftment was noted in older recipients; this reconstitution however, was also age‐dependent. Migration from the peritoneum to systemic circulation was necessary for serum IgM production as shown by the presence of donor antibody‐secreting cells in the host spleen. Host lymphocytes also influenced the success of i.p. transplantation as severe combined immune‐deficient mice, regardless of age, exhibited donor serum IgM production. Recipient age, Igh allotype, and immune‐deficiency were found to have an impact on the ability of i.p.‐transferred PerC B cells to restore B‐cell function in XID mice.