Reports that protein kinase C is inhibited by sphingosine and other long-chain amines and the suggestion that promotion of mammary carcinogenesis by dietary fat is mediated by protein kinase C prompted us to investigate the effects of a long-chain amine, 1-octadecylamine, on mammary carcinogenesis induced by 7,12-dimethylbenz[a]anthracene in rats fed a high-fat diet. Rats fed the amine sulfate at a level of 0.01% in a semipurified diet containing 20% corn oil developed more tumors than those fed the high-fat diet alone, although body weight gain was inhibited slightly. Rats fed the amine sulfate at 0.1% of the diet developed very few tumors compared with those fed either the high-fat diet or a low-fat diet containing 5% corn oil. At the higher level, the C18 amine also caused a marked inhibition of body weight gain.