The highest diamine oxidase activity is contained in small-bowel mucosa and, after heparin administration, the enzyme is released by the intestine into the plasma. Previous experimental studies showed that measurement of plasma postheparin diamine oxidase activity is a sensitive test for quantitating the length and severity of small-bowel mucosal injury. On this basis, we measured plasma diamine oxidase activity in celiac disease, a condition characterized by a loss of mature enterocyte mass. Twenty-five untreated celiac patients, 21 celiac patients on a gluten-free diet, 16 patients with small-bowel diseases other than celiac disease (abnormal controls), and 18 healthy controls were studied. Diamine oxidase activity was measured using [14C]putrescine as substrate and expressed as units per milliliter of plasma. Basal diamine oxidase levels in controls and patients were too low for significant differences between the groups to be detected. After preliminary experiments in which, on separate occasions, heparin was intravenously administered at doses of 75 and 150 units/kg and in which the second blood sample was taken 10 and 30 min after heparin injection, it was decided to use the 150 unit/kg dose and to measure plasma diamine oxidase activity in the blood sample taken 10 min after heparin stimulation in all the remaining subjects taking part in the study. Postheparin diamine oxidase levels were significantly lower in untreated celiac patients (mean 1.53 units/ml) than in healthy controls (mean 5.85), treated celiac patients (mean 4.82), and abnormal controls (mean 2.62). Except in three patients, no overlap between healthy controls and untreated celiac patients was observed. No significant difference was detected between healthy controls and treated celiac patients.(ABSTRACT TRUNCATED AT 250 WORDS)