Colon cancer was induced in 40 Sprague Dawley rats using a 10-week course of 1,2 dimethylhydrazine (DMH). Twenty animals received cimetidine in their drinking water, commencing 5 weeks after concluding the course of DMH. After five weeks treatment of the animals were sacrificed and the colon and rectum excised. Tumours were assessed histologically for depth of invasion, inflammatory cell response and stained for Proliferating Cell Nuclear Antigen (PCNA), as a measure of tumour proliferative index. PCNA staining was measured using a computerized image analysis system. There were 25 tumours in the cimetidine treated group and 20 in controls. In the control group, 10% of the tumours were benign, 35% malignant polyps, 40% invading through submucosa and 15% invading through the bowel wall, as opposed to 40%, 44%, 8% and 8%, respectively in the cimetidine group (Chi squared test: P = 0.002). The mean proliferative index for control tumours was 27.9% and for the cimetidine tumours 23.1% t test: P = 0.002). It is concluded that cimetidine inhibits colon cancer cellular proliferation and slows early tumour invasion in this animal model.