Patients with Crohn's disease of the distal ileum show increased permeability to hyaluronan and increased release of histamine and complement components in uninvolved parts of the proximal jejunum. These abnormalities are related to disease activity, and are not found in first-degree relatives. Increased synthesis of prostaglandins has been observed in inflamed areas of the intestine in active Crohn's disease. Our purpose was to measure luminal prostaglandin release in patients with active and inactive Crohn's disease and their first-degree relatives. Twenty-four patients with Crohn's disease of the distal ileum (10 in remission and 12 with inflammatory activity) and 17 of their first-degree relatives were included and compared with healthy control subjects (n = 39). Ten centimetres of the proximal jejunum was isolated between balloons as described previously and perfused with a balanced electrolyte glucose-containing solution. Luminal concentrations of PGE2 and albumin were measured and their luminal release was calculated. Luminal release of PGE2 was significantly higher in patients with Crohn's disease than in control subjects [69.7 +/- 11.5 and 34.0 +/- 4.7 pg/cm per h (3.7 +/- 0.6 and 1.8 +/- 0.3 ng/L), respectively, P < 0.01]. The PGE2 levels, however, were not positively correlated to disease activity. Furthermore, there was a modest, but significant increase in luminal PGE2 in first-degree relatives [53.6 +/- 7.0 pg/cm per h (2.9 +/- 0.4 ng/L), P < 0.05]. These changes were not accompanied by significant changes in luminal permeation of albumin.(ABSTRACT TRUNCATED AT 250 WORDS)