Secretory IgA (S-IgA), an immunoglobulin present in secretions, prevents the adherence of bacteria to mucosal cells and is the principle component of the gut mucosal defense system. The purpose of this study was to determine whether the route of nutrient administration affects S-IgA. Twenty-five female Fisher rats were randomized into three groups. Groups I and II were fed an isonitrogenous, isocaloric standard hyperalimentation solution, Group I intravenously and Group II via a gastrostomy. Group III (control) was fed rat chow and water ad lib. Since bile is one of the principle sources of S-IgA, animals had biliary T-tubes placed for sampling of bile every 4 days. At day 16, Group I animals were fed rat chow and water for an additional 8 days. S-IgA was measured by the ELISA immunoassay. Results indicated at day 16 that the S-IgA level in mg/ml of Group I was 1.1 +/- 0.2, while the S-IgA in Groups II and III was 2.2 +/- 0.6 and 2.2 +/- 0.26, respectively. Furthermore, the S-IgA level in Group I after 8 days of enteral feeding rose to 1.8 +/- 0.4. The difference in S-IgA levels between enterally and parenterally fed rats suggests that an important defense barrier is compromised during parenteral hyperalimentation. Rats fed the same nutrients by gastrostomy maintained S-IgA levels better than rats fed the same nutrients intravenously. The rapid return to normal levels after resumption of enteral feeding suggests that the intraluminal presence of foodstuffs is essential for maintenance of S-IgA.