The number of intraepithelial lymphocytes (IELs) is often increased in the terminal ileum of patients with immune-mediated inflammatory diseases of the colon. However, data regarding their number in normal ileal mucosa of asymptomatic patients are lacking. We aimed to establish the acceptable range of IELs in biopsy specimens of normal ileal mucosa.Ileal mucosal biopsy specimens obtained during colonoscopy of 61 asymptomatic patients without endoscopic or pathologic evidence of colitis were immunostained for CD3 to assess the number of IELs present in each specimen. CD3+ lymphocytes were counted in 3 well-oriented villi and results expressed as the average for each biopsy specimen. The study group included 25 males and 36 females, ranging in age from 10 to 84 years (mean, 44.4 years). The mean +/- SD number of ileal CD3+ cells per 100 enterocytes for the group was 3.8 +/- 2 (median, 3; range, 0-9). In addition, there was a significant inverse relationship between the number of villus IELs and increasing age.Occasional IELs (approximately 4/100 villus enterocytes) are normally present in ileal biopsy specimens from asymptomatic patients without colitis. One should avoid overinterpreting the importance of occasional IELs in ileal biopsy specimens from asymptomatic patients.