A prospective endoscopic and histologic study of terminal ileum and colorectum in 211 patients with seronegative spondylarthropathy revealed macroscopic inflammatory lesions varying from erythema to superficial erosions in 30% of the patients and microscopic inflammation in 61%. Two types of inflammation were observed: an acute inflammation resembling an infectious enterocolitis and a chronic inflammation. In idiopathic reactive arthritis both types of inflammation were equally present, whereas chronic inflammation predominated in patients with ankylosing spondylitis. In 32% of patients with chronic inflammation, the lesions particularly resembled early Crohn's disease. Repeat ileocolonscopy on 19 patients demonstrated a parallel evolution of joint symptoms and histologic lesions. All patients with acute inflammation went into clinical and histologic remission, whereas lesions persisted in patients with Crohn-like inflammation. In patients with chronic inflammation, remission and persistence were observed equally. This study identified a group of patients with seronegative spondylarthropathy which, even in the absence of gastrointestinal symptoms, showed evidence of gut inflammation, probably inducing an increased gut permeability with transgression of the oral tolerance and absorption of provocative antigens into the circulation. It is also possible that both diseases reflect a common underlying process.