Background: Bovine colostrum is a rich source of nutrients, antibodies and growth factors. Aim: To examine the efficacy of colostrum enemas in the treatment of distal colitis using a randomized, double-blind, controlled protocol. Methods: Fourteen patients (eight female), with a mean age of 45 years (range, 16-75 years) and mild to moderately severe distal colitis (Powell-Tuck scoring system), received colostrum enema (100 mL of 10% solution) or placebo (albumin solution) b.d. for 4 weeks. Both groups also received mesalazine (1.6 g/day) or, if already taking it, had a dose increment of 1.6 g/day. Disease activity was documented at 0, 2 and 4 weeks. Results: After 4 weeks, the colostrum group showed a mean reduction in symptom score of -2.9 (95% confidence interval (CI), -5.4 to -0.3), whereas the placebo group showed a mean response of +0.5 (95% CI. -2.4 to +3.4). The histological score improved in five of the eight patients in the colostrum group (mean response. -0.9; 95% CI, -1.69 to -0.03), whereas the histological scores only improved in two of the six patients in the placebo group (mean response, 0.2: 95% CI, -2.4 to +2.6). Conclusions: Bovine colostrum enema shows potential as a novel therapy for left-sided colitis with additional benefits over using mesalazine alone. Further studies appear to be warranted.