The influence of caffeine consumption on the development of 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas in BD2F1 female mice and spontaneous mammary carcinomas in nulliparous C3H mice was examined. Caffeine (250 and 500 mg/liter of drinking water) was administered to BD2F1 mice commencing 1 week after a series of 6 weekly 7,12-dimethylbenz(a)anthracene intubations, until experiment termination. Caffeine was administered to C3H mice (via drinking water) commencing at 8 weeks of age to experiment termination. In BD2F1 mice receiving 250 and 500 mg of caffeine, mammary carcinoma multiplicity (number of mammary carcinomas/mouse) was increased by 20 and 40%, respectively. In C3H mice receiving 250 and 500 mg caffeine, mammary carcinoma multiplicity was increased by 13 and 117%, respectively. In both BD2F1 and C3H mice, the higher dose level of caffeine resulted in a significant (P less than 0.05) increase in mammary carcinoma multiplicity. Caffeine consumption did not significantly effect the percentage of mice bearing mammary carcinomas or the mean latency period of mammary tumor appearance. In a second series of studies, the influence of caffeine consumption on mammary gland development in female BALB/c mice was assessed in vivo and in vitro (organ culture). In mice consuming caffeine (500 mg/liter of drinking water), mammary gland development was significantly (P less than 0.05) increased compared to control mice; this difference in mammae development was more conspicuous in mice treated with mammotropic hormones. In the organ culture studies, mammary glands derived from caffeine (500 mg/liter of drinking water) consuming BALB/c mice were more responsive in vitro to a mammotropic hormonal developmental growth stimulus than were mammae derived from control mice (P less than 0.05). These results provide evidence that caffeine consumption can enhance mammary tumorigenesis in C3H and carcinogen-treated BD2F1 female mice and, in addition, enhance developmental growth of the normal female mouse (BALB/c) mammary gland.