Despite extensive research, the pathogenesis of inflammatory bowel disease (IBD) is still unclear. Immunological disorders have been described in patients with both Crohn's disease (CD) and ulcerative colitis (UC). In this work serum samples collected from 58 patients with CD and 55 patients with UC were tested in ELISA against a panel of nuclear and cytoplasmic proteins and peptides in order to determine whether specific autoantibodies are produced in these patients. Low levels of IgG antibodies to histones H1, H2A, H2B, H3, and H4, to Hsp-70 and ubiquitin stress proteins, Ro/SSA and La/SSB proteins and myosin were detected in some of these sera. In contrast, the following antibodies of IgG isotype could be much more frequently demonstrated: antibodies to ubiquitinated H2A (U-H2A) peptide T4 (51.7% in CD; 18.2% in UC), antibodies to the zinc-finger peptide F2 of poly-(ADP-ribose polymer)ase (PARP) involved in DNA repair (58.6% in CD; 25.5% in UC) and actin antibodies (43.1% in CD; 7.3% in UC). In a follow-up study of 12 patients with CD and UC (75 additional samples), we found IgG antibodies to several histone peptides occurring essentially in the serum of patients with CD. Although we found no obvious correlation between the presence or level of these various antibodies and C-reactive protein, or the location of the disease, in a number (but not all) of patients, we observed a strikingly good relationship between antibodies to histone peptides, U-H2A peptide T4, and PARP peptide F2 and the Crohn's disease activity index. The mechanism of induction of these antibodies still remains obscure.(ABSTRACT TRUNCATED AT 250 WORDS)