Campylobacter jejuni is a common cause of human gastrointestinal disease worldwide. Despite the prevalence of C. jejuni infections, the mechanisms of C. jejuni pathogenesis remain ill-defined. Invasion of the cells lining the intestinal tract is hypothesized to be essential for the development of C. jejuni-mediated enteritis. Recent studies in our laboratory have revealed that C. jejuni secrete proteins, termed Cia for Campylobacter invasion antigens, upon incubation with human intestinal cells. A mutation in one of the genes encoding a secreted protein resulted in an invasion-deficient phenotype. The purpose of this study was to identify a component capable of stimulating the synthesis and secretion of the Cia proteins from C. jejuni. Here, we report that these processes can be induced upon incubating C. jejuni in medium supplemented with fetal bovine serum. The synthesis and secretion of the Cia proteins were not affected by heat-treatment of the fetal bovine serum, indicating that the stimulating molecule in serum is heat stable. The stimulatory molecule was not unique to fetal bovine serum as sera from other sources including human, pig, sheep, goat, rabbit, mouse, and chicken also induced the synthesis and release of the Cia proteins. These findings indicate that the synthesis and secretion of the Cia proteins can be induced in a cell-free system by incubating C. jejuni in serum-supplemented tissue culture medium.