The secretion of the neutral protease plasminogen activator (PA) by cultured macrophages (M phi) was studied in hospitalized patients suffering from chronic inflammatory bowel disease (IBD). There was markedly enhanced secretion of PA by M phi derived from circulating monocytes of the IBD population (18) compared to an age-matched population (16) which was not afflicted by intestinal disease (P less than 0 . 001). Mean M phi PA activity was greater in the population of 11 Crohn's disease patients (P less than 0 . 01) than in a group of seven ulcerative colitis sufferers (P less than 0 . 05) when compared to the control population. While both the treated and untreated hospitalized IBD populations showed increased M phi PA specific activity, results for the nine untreated patients (5 . 56 +/- 1.14 units/micrograms M phi DNA) were substantially higher than those found in the treated IBD population (2 . 91 +/- 0 . 62 units/micrograms M phi DNA) (P less than 0 . 01). These findings reflect the activity of M phi in IBD and suggest a means by which tissue injury is mediated in these conditions.