The activity of platelet-activating factor (PAF) acetylhydrolase in biopsy specimens of intestinal mucosa was compared in patients with Crohn’s disease (n = 11) and controls (n = 6). In addition, PAF acetylhydrolase activity was determined in the plasma of Crohn patients (n = 30) and healthy subjects (n = 35). The activity of PAF acetylhydrolase in mucosal samples from the distal ileum was significantly lower in Crohn patients than in control patients (p 150) had a significantly lower PAF acetylhydrolase activity in plasma, as compared to patients in clinical remission (symptomatic index < 150; p < 0.02), and as compared to healthy subjects (p < 0.001). PAF acetylhydrolase activity in plasma increased within 4 months after bowel resection (P < 0.05). These findings indicate that the PAF acetylhydrolase activity is decreased in the ileal mucosa of patients with Crohn’s disease and that PAF acetylhydrolase activity in plasma is inversely related to disease activity in Crohn’s disease. The possibility that PAF acetylhydrolase is one factor of importance for protecting the intestinal mucosa against PAF-mediated inflammation is inf