Most IgA plasma cells in the digestive tract are thought to derive from gut-associated lymphoid tissue, whereas IgA plasma cells in the respiratory mucosa are thought to originate largely in bronchus-associated lymphoid tissue. However, previous work has also shown that IgA antibodies to gut antigens can be detected in immunocytes of the bronchial mucosa and in bronchial secretions after appropriate stimulation via the gut. To analyze the cellular origin of such respiratory antibodies, mice were orally immunized with ferritin for 40 days and then segregated for intrabronchial challenge as follows: one group was given saline, another group Formalin-fixed Escherichia coli as a nonspecific challenge, and a third group ferritin. Lungs and intestines from these animals were then examined by immunofluorescence for the presence of plasma cells containing particular isotypes of antibody to ferritin. Animals fed ferritin and given saline or E. coli intrabronchially showed a greater than 6-fold increment in IgA antiferritin plasma cells in the bronchial mucosa, compared to animals which had not received ferritin, whereas orally immunized animals challenged intrabronchially with ferritin showed a greater than 15-fold increase. In other experiments, ferritin-naive animals transfused with mesenteric node cells that were obtained from donors that had been orally immunized with ferritin and were already committed to IgA production showed a 4-fold or greater increase in IgA antiferritin plasma cells in respiratory mucosa after intrabronchial challenge with ferritin when compared to recipients of peripheral node cells from the same donors or to recipients of mesenteric node cells that had not been specifically boosted intrabronchially. These results suggest that immunologically specific IgA immunocytes from gut-associated lymphoid tissue can migrate to the respiratory mucosa after oral immunization, and that migration and/or local cell division are enhanced by subsequent intrabronchial challenge. In providing further evidence for interrelations between gut-associated and bronchus-associated lymphoid tissue, the findings lend added support to the overall concept of a generalized secretory immune system.