The purpose of the present study was to determine the effects of caffeine on the mandibles of newborn rats whose dams were given a normal diet (200 g protein/kg diet) compared with those given a high-protein diet (400 g protein/kg diet) during gestation. A total of twenty pregnant Sprague-Dawley rats were randomly divided into four groups of five each. Starting on day 7 of gestation, groups 1 and 2 were fed on control and high-protein diets respectively, and groups 3 and 4 were pair-fed with groups 1 and 2 respectively, but with caffeine added to their diets. The caffeine supplement was 20 mg/kg body-weight. At birth, pups were killed and various measurements of their mandibles were made. The mandibular weights, calcium contents, and alkaline (EC 3.1.3.1) and acid (EC 3.1.3.2) phosphatase activities of the group given the caffeine-supplemented control diet were significantly lower than those of the corresponding unsupplemented group. Alkaline and acid phosphatase activities, collagen synthesis and hydroxyproline contents of the caffeine-supplemented high-protein group were greater than those of the corresponding unsupplemented group, whereas Ca and protein contents of the caffeine-supplemented high-protein group were lower than those of the corresponding unsupplemented group. There were no significant differences in plasma caffeine levels for either dams or pups between the caffeine-supplemented control and high-protein groups. The effects of caffeine on the development of fetal mandibles are apparently modified by different levels of maternal dietary protein.