In this communication, a vast array of studies designed to examine the relationship between dietary fat and experimental mammary gland tumorigenesis was reviewed and critiqued. It is clear, as reported by many laboratories, that as the fat content of the diet is increased from a low or standard level to a high level, a consistent and substantial increase in the development of rodent mammary gland tumors is observed. The longer the duration the high-fat diet is fed, the greater the enhancing effect on tumorigenesis. Furthermore, the stimulatory effect of a high-fat diet is observed even when fed commencing late in an animal's life. A multitude of studies also have provided evidence that the type of fat can markedly influence the development of rodent mammary gland tumors. In general, high dietary levels of unsaturated fats (e.g., corn oil, sunflower-seed oil) stimulate this tumorigenic process more than high levels of saturated fats (e.g., beef tallow, coconut oil); diets rich in certain fish oils (e.g., Menhaden oil, Max EPA) are often the most inhibitory to this tumorigenic process. Importantly, however, supplementation of saturated fat or fish oil diets with modest amounts of unsaturated fats, e.g., corn oil, often negates the mammary tumor inhibitory activities of these fats. Thus, rather extreme differences in the types of fat are required for a differential in mammary gland tumorigenesis; common proportionate blends of different fats of animal, plant, and/or fish origin are often unable to differentially influence this tumorigenic process. Diets rich in monoenoic fatty acids, e.g., those containing high levels of olive oil, have been examined in a number of studies; results from these studies have been inconsistent. A number of reports suggest that the increase in development of mammary tumors in rodents fed a high-fat diet, compared with those fed a low-fat diet, is due to specific metabolic activities of the fat per se, activities independent of a caloric mechanism. Careful analysis of these reports suggest that such a conclusion may not be totally warranted. Indeed, persuasive evidence is accumulating indicating that the major mammary tumor development enhancing activities of a high-fat diet may be via a caloric (energy) mechanism. Caloric restriction, even in animals fed a high-fat diet, significantly suppresses mammary tumor development. Even mild caloric restriction (e.g., 12%) can significantly suppress development of mammary tumors in rodents.(ABSTRACT TRUNCATED AT 400 WORDS)