Intranasal (i.n.) immunization is a very effective route for inducing mucosal immunity, but the cellular mechanism responsible for regulating and disseminating these responses is not fully understood. The authors studied the role of nasal lymphoid tissue (NALT) as a mucosal inductive site by using highly purified NALT cells obtained by a new method of mechanical isolation. The NALT cells, like Peyer's patch (PP) cells, were smaller in size and less granular than lymphocytes from salivary glands (SG) and small intestinal lamina propria (LP). The NALT cells isolated from i.n. immunized mice contained antigen-specific antibody-secreting cells (ASC) predominantly of immunoglobulin (Ig)A isotype, similar to those also recovered from salivary glands in a time course study. However, the higher proportion of smaller sized sports formed by NALT cells in ELISPOT assays suggested that these cells were less differentiated precursors of those found in salivary glands. This was supported by the fact that after i.n. immunization, IgA ASC appeared in NALT, as well as in mucosal effector sites SG and LP, but none or very few in another mucosal inductive site, PP. In contrast, after intragastric (i.g.) immunization, IgA ASC were detected in PP, along with the SG and LP, but none or very few in NALT. Furthermore, after i.n. immunization, lymphocytes from NALT but not PP proliferated in response to the specific antigen in culture. These findings imply that NALT served as an inductive site for IgA antibody responses at mucosal effector sites.