Polymorphism of the third component of complement (C3), occupying a key position in cascade reactions, was investigated in 125 consecutive outpatients, 53 with Crohn's disease and 72 with ulcerative colitis. A sample of 1378 randomly selected healthy volunteers of Danish origin served as controls. Occurrence of the F and FS phenotype of C3 (C3F and C3FS ) was increased in the group of Crohn's disease patients (chi 2 = 2.80, p less than 0.05, one-tailed test) and in a subgroup of Crohn patients with the gastrointestinal disease process confined to ileum (chi 2 = 6.91, p less than 0.01). C3 phenotype distribution was unaffected in ulcerative colitis. Only S and F alleles of C3 ( C3S and C3F) were recognized and C3F frequencies were 0.33 in Crohn patients with small bowel disease, 0.23 in all Crohn patients, 0.18 in ulcerative colitis patients and 0.17 in healthy volunteers. The results are compatible with a positive association of the C3F gene and Crohn's disease located in the small bowel.