The mammary tumor-promoting effects of a high-fat (HF) diet (23%, w/w) containing a 3:1 mixture of medium-chain triglycerides (MCT) and corn oil were compared with those of a low-fat (LF) corn oil diet (5%) and a HF: corn oil diet (23%, w/w). It was found that the ingestion of MCT in a HF diet resulted in no detectable tumor-promoting effects in animals initiated with the potent mammary carcinogen N-nitrosomethylurea. Total palpable mammary tumor incidence was 60% in the HF:corn oil plus MCT group, 66% in the LF:corn oil group, and 87% in the HF:corn oil group (p less than 0.03 and p less than 0.06, respectively). However, when palpable adenocarcinomas only were counted, differences in incidence between groups were not statistically significant, HF:MCT (57%) versus HF:corn oil (77%), p less than 0.08. Mean time to first tumor (days) was 122 +/- 40 (S.D.) in the MCT, 117 +/- 36 in the LF:corn oil groups, and 86 +/- 23 in the HF:corn oil group. The cumulative tumor incidence curves were similar for the MCT and LF:corn oil groups (p less than 0.9); however, both curves were significantly different from that of the HF:corn oil group (p less than 0.0099). No differences were found in tumor multiplicity, tumor size, or body weight gain in any of the treatment groups. Assay of serum total cholesterol and triglycerides showed that consumption of 23% corn oil diet significantly depressed serum cholesterol (but not triglyceride) levels compared to the LF:5% corn oil- and the HF:MCT-containing diets. Analysis of serum fatty acid profiles indicated that animals fed 23% corn oil exhibited twice the amount of linoleic acid (C18:2) as did those fed either 5% corn oil or MCT. Differences in other fatty acids were of a much lesser magnitude. These results indicate that the mammary tumor-promoting effect of a HF diet can be diminished by substituting saturated MCT for the more common longer-unsaturated-chain triglycerides. In addition, they suggest an association between promotion of mammary cancer and elevated levels of linoleic acid in serum lipids.