We compared the effects of neonatal appendectomy in rabbits on total Ig and antigen (Ag)-specific Ig levels in the serum and gut, and on plasma cell numbers in the small intestine in response to intraperitoneal (i.p.) and intraduodenal (i.d.) immunizations with ovalbumin (OVA). Animals were sacrificed after 9 weeks. Antibodies (Abs) in the duodenum were collected and quantified by enzyme-linked immunosorbent assay (ELISA) while plasma cells were quantified by double immunofluorescent staining. Appendectomy markedly reduced total intestinal IgA (P < 0.0006), IgM (P < 0.003), and IgG (P < 0.05) relative to controls, whereas total serum Ig levels were not lowered significantly. Moreover, appendectomy nearly ablated OVA-specific IgA (P < 0.007) in the gut and severely depleted OVA-specific IgG in the gut (P < 0.03) and serum (P < 0.007). The sharp decreases in total IgA and anti-OVA IgA were paralleled by decreases in total IgA+ plasma cells (P < 0.0005) and OVA-reactive IgA+ plasma cells (P < 0.05). These results support a major role of the rabbit appendix in seeding the intestinal lamina propria with plasma cell precursors, especially those producing IgA.