Oils derived from the peel of four citrus fruits, sweet orange, lemon, grapefruit, and lime, were found to cause epidermal hyperplasia in mice of the inbred strain 101. These oils were tested for tumor-promoting activity by weekly application to the mouse skin after a single application of 300 µg. of 9,10-dimethyl-1,2-benzanthracene (DMBA): all gave rise to skin papillomas after 5 to 12 weeks. Several malignant skin tumors have also arisen, and more are expected as observation continues. Dilution of orange oil with acetone reduced the tumor-promoting effect. Undiluted orange oil promoted tumors in mice previously treated topically or parenterally with urethan. Orange oil, undiluted or diluted with acetone, was not carcinogenic for mouse skin. Normal mice and urethan-pretreated mice were given 7 intradermal injections of undiluted orange oil; no tumors arose during a 30-week observation period. Preliminary experiments indicate that the promoting activity of orange oil is probably due to its content of d-limonene, which constitutes more than 90 percent of the oil, and not to the terpene alcohols and other oxygenated compounds present. Papillomatous tumors of the urethral orifice were seen in 7 mice: 4 treated with DMBA and diluted orange oil, 2 with diluted orange oil only, and 1 with DMBA and the nonterpene fraction of orange oil. The diluent, acetone, probably facilitated the absorption of the active component of orange oil since no urethral tumors arose in mice painted with the undiluted oil. The experimental production of these tumors has not, to our knowledge, been reported previously.