The effects of corn oil and beef tallow on the proliferation of colon mucosal cells in rats were investigated. In protocol 1, rats were fed diets containing 12 or 38% kJ from fat supplied by either corn oil or beef tallow. Colon crypt column cell number was examined histologically. The source of dietary fat had no effect on the number of cells per crypt column, but rats fed 38% fat had significantly fewer cells per crypt column in the proximal colon than rats fed 12%. Protocol 2 examined the effects of diets containing corn oil or beef tallow at 12, 30, or 37% kJ on the percentage of colon cells in phases of the cell cycle using flow cytometry and expression of proliferating cell nuclear antigen (PCNA). Rats fed corn oil had more cells in S phase compared to rats fed beef tallow. Rats fed 30 or 37% fat had more cells in G1 and fewer cells in G2 + M compared to rats fed 12%. Animals consuming the 12% corn oil diet or the 37% beef tallow diet had the fewest colon cells expressing PCNA, while those animals consuming the 37% corn oil diet or the 12% beef tallow diet had the greatest number of cells expressing PCNA. Based on combined interpretation of PCNA and cell cycle phases, the results suggest that diets high in saturated fat result in reduced colon cell proliferation whereas diets high in unsaturated fat do not.