Prior work has demonstrated that food restriction of mice markedly suppresses 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion of skin papillomas and adrenalectomy prior to initiating food restriction completely reverses the tumor inhibitory effect of underfeeding. In the present experiment the effect of food restriction, with or without prior adrenalectomy, on 7,12-dimethylbenz[a]anthracene (DMBA)-induced lung tumor development in A/J mice was explored. Food restriction (27%), beginning 3 weeks after a single oral dose of 0.5 mg DMBA and continued for the duration of the experiment (14 weeks), significantly inhibited lung adenoma development, whereas adrenalectomy 2 weeks before initiating food restriction abolished the tumor inhibitory effect of underfeeding and also enhanced tumor development in the ad libitum fed mice. Plasma corticosterone levels were significantly elevated in food-restricted A/J mice, whereas plasma dehydroepiandrosterone (DHEA) levels showed no apparent change. These studies suggest that adrenal gland secretory products may play a general role in the tumor preventive effect of food restriction in laboratory mice.