We have investigated the ability of the gut-associated lymphoid tissues (GALT) to react against standard antigens presented via different routes of administration. When antigens were presented directly to GALT, either by an injection into the Peyer's patches or via a mechanically damaged lamina propria, a rapid and vigorous immune response ensued. This was manifested systemically as an antigen-specific humoral antibody response in the serum and locally as an antigen-specific immunoglobulin A response in the bile. These results indicate that GALT is capable of reacting to foreign materials penetrating the gut wall. Additional experiments demonstrated that the extended feeding of degraded iota carrageenan, a material known to produce non-specific mucosal inflammation, caused GALT to react to antigenic molecules present within the gastro-intestinal tract and enhanced both serum and biliary antibody responses against specific gut commensal microorganisms. The immunological significance of these observations is discussed.