Using CT as the test antigen, we sought 1) to learn whether primary immunization at 1 mucosal site caused priming of distant nonstimulated mucosae, 2) to study the role of migrating memory cells in the dissemination of mucosal priming, and 3) to compare disseminated priming with priming that occurs at the site of initial immunization. CT given i.c. or i.d. caused priming in tracheal and nonexposed enteric mucosae; i.t. immunization, however, did not cause detectable enteric priming. Adoptive transfer of immune TDLs showed that priming was conveyed by migrating memory cells. These appeared to be of 2 types: those that recirculated briefly before settling in MALT, and those that continued to recirculate until recruited by antigen to the site of mucosal challenge. Both types were required for secondary responses at mucosae distant from the site of priming. The time-course of disseminated mucosal priming resembled that of priming at the site of initial CT exposure, both lasting at least 16 wk. Disseminated priming persisted better in jejunal than tracheal mucosa, suggesting that the subgroup of memory cells that did not continue to recirculate settled preferentially in jejunal MALT. Disseminated priming supported smaller challenge responses than priming at the site of initial CT exposure did, suggesting that sessile memory cells also contributed to the latter process. These observations extend the concept of a "common mucosal immune system" to include cellular dissemination of mucosal priming, but also show quantitative differences between local and disseminated priming that probably reflect the patterns of distribution of migrating and sessile memory cells.