Background : Surgical resection of Crohn’s disease is followed by early recurrence in a high percentage of patients. Mesalazine has been shown to be effective in the prevention of post‐operative recurrence, but some 50% of patients under treatment recur at 3 years of follow‐up. Aim : To establish whether the mucosal concentration of mesalazine might affect the development of post‐operative recurrence. Methods : Colon‐ileoscopy was performed in 25 consecutive patients resected for Crohn’s disease. The mean time from surgery was 14 months. After the operation, all patients were taking oral mesalazine (Asacol, 2.4 g/day). Ten patients showed signs of endoscopic recurrence (apthae, ulcers, narrowing of the lumen) in the neoterminal ileum, five of whom also showed juxta‐anastomotic colonic involvement. Fifteen patients were free of recurrence. At endoscopy, four biopsies were taken from the perianastomotic area (two specimens at the ileal site and two specimens at the colonic site of the anastomosis). The specimens were weighed and immediately frozen at −80 °C. Mesalazine concentration (ng/mg) was measured in tissue homogenates by high‐ performance liquid chromatography with electrochemical detection. Fisher’s exact test was used for the statistical analysis. Results : The mean value of mucosal mesalazine concentration, expressed as ng/mg of tissue, was significantly lower in patients with recurrence than in those without recurrence both in the ileum (mean ± s.d.: 21.6 ± 28.3 vs. 70.9 ± 47.4; P = 0.007) and in the colon (25.8 ± 26.4 vs. 60.3 ± 32.5; P = 0.010). Conclusions : The mucosal conentration of mesalazine in the juxta‐anastomatic area is significantly lower in patients with recurrence than in those free of recurrence. These data could suggest an association between mucosal mesalazine concentrations and the clinical effectiveness of the drug.