Crohn's disease and ulcerative colitis show a familial aggregation. The role of antinuclear autoantibodies, which occur in both diseases, remains to be defined. In 76 patients with Crohn's disease, 61 patients with ulcerative colitis, 105 first-degree relatives of patients with Crohn's disease, 101 first-degree relatives of patients with ulcerative colitis, and 40 healthy unrelated controls antinuclear autoantibodies were detected by indirect immunofluorescence. Existence of autoantibodies was correlated with clinical features. Eighteen percent of patients with Crohn's disease (14/76), 43% of patients with ulcerative colitis (26/61), 13% of relatives of patients with Crohn's disease (14/105), 24% of relatives of ulcerative colitis patients (24/101), and 2% of the healthy controls (1/40) were positive for antinuclear autoantibodies. The difference between controls and patients and the first-degree relatives of patients with ulcerative colitis, respectively, was statistically significant (P < or = 0.0144). In ulcerative colitis, the existence of antinuclear autoantibodies was negatively correlated with immunosuppressive therapy or extraintestinal manifestations (P = 0.0004 and 0.0273, respectively). Antinuclear autoantibodies may represent a factor disposing to the development of ulcerative colitis.