Dietary fat and calcium have been found to affect significantly the proliferative status of the mammary glands. Female mice (3-week-old C57BL/6J) were given either a low or high corn oil diet (3 or 30% by weight). One, 2, or 4 weeks after the dietary intervention the animals were given injections of [3H]thymidine and/or colchicine; 2 h later their thoracic mammary glands were removed and processed for histology and autoradiography. Animals on the high corn oil diet had an increased labeling index of both terminal ducts and mature ducts compared to the control group at each time (i.e., 10.1 +/- 2.1 versus 4.8 +/- 0.9% at 2 weeks). This effect of a high corn oil diet was evident on the mammary glands of animals at various ages. Animals on a high beef tallow diet also had a high labeling index. This effect of a high fat diet appeared to be reduced by dietary calcium. The labeling index for terminal ducts of animals on high corn oil diet decreased from 14.1 +/- 3.8, 11.9 +/- 3.4 to 8.5 +/- 1.8 and high beef tallow from 13.6 +/- 3.6, 11.4 +/- 0.7 to 9.5 +/- 1.3 for calcium levels of 0.1, 0.5, and 1.0%, respectively. Mitotic indices followed the same trend. These studies demonstrate that a high fat diet affects the proliferative status in the mouse mammary glands in a short period of time and that this effect can be reduced by dietary calcium.