The role of Peyer's patches in the local intestinal and serum antibody responses to keyhole limpet haemocyanin (KLH) was studied in rabbits with chronically isolated ileal loops. Four weekly doses of 400 microgram KLH were administered into loops prepared with and without Peyer's patches. Isotype-specific IgA and IgG anti-KLH in loop secretions collected twice each week and in sera collected weekly were assessed by enzyme-linked immunosorbent assay. Fluid IgA anti-KLH in loops without Peyer's patches first showed a statistically significant increase on day 25, 1 week later than control loops with Peyer's patches. However, some animals in the group without Peyer's patches showed a rise as early as day 7, and the differences from controls were not statistically significant at any time. No statistically significant rise in fluid or serum IgG anti-KLH occurred in either group. Thus, Peyer's patches were not essential for local intestinal antibody response to KLH, a soluble macromolecular antigen. The findings suggest that the innumerable small lymphoid nodules in the gastrointestinal tract, or other mechanisms of antigen processing, play an important role in local intestinal immune responses.