Parenteral immunization of rats with cholera toxoid had both priming and suppressive effects upon the antitoxin response in jejunal lamina propria to locally applied toxoid/toxin. Priming was detected when parenteral toxoid was given i.p. but not i.v. or s.c., was enhanced by Freund's adjuvant, and appeared to reflect enhanced encounter of i.p. antigen with IgA-committed lymphocytes in extra-intestinal mucosa-associated lymphoid tissue. In contrast, suppression followed parenteral toxoid given i.p., i.v., or s.c.; suppression was antigen specific and lasted at least 16 weeks. Parenteral toxoid suppressed both primary and secondary types of mucosal antitoxin responses, ultimately preventing the generation of antitoxin-containing immunoblasts from Peyer's patches. Since suppression followed parenteral immunization by routes that did not provoke mucosal priming, it was, at least in those instances, not simply a regulatory consequence of mucosal priming. These results support the notion that priming and suppression of a specific mucosal immune response are independent effects of parenteral immunization that are probably determined by the distribution of antigen to mucosa-associated and systemic lymphoid tissue, respectively.