The sexual dimorphism of the corpus callosum has remained controversial since the original report by de Lacoste-Utamsing and Holloway in 1982, for several reasons: (1) measurements have been performed in a variety of ways in different laboratories, in part because published reports frequently do not describe the methodology in detail; (2) despite known age-related changes during both childhood and adulthood, no investigators have explicitly age-matched subjects; and (3) the size and shape of corpora callosa vary considerably among individuals, requiring large sample sizes to demonstrate significant sex differences. Therefore, we have examined magnetic resonance images for 24 age-matched children and 122 age-matched adults for possible sex differences in the corpus callosum. While we observed a dramatic sex difference in the shape of the corpus callosum, there was no conclusive evidence of sexual dimorphism in the area of the corpus callosum or its subdivisions. Utilizing several criteria, there were significant sex differences in shape: subjective evaluation indicated that the posterior region of the corpus callosum, the splenium, was more bulbous shaped in females as a group and in women, and more tubular-shaped in males as a group and in men; mathematical evaluation confirmed this observation in that the maximum width of the splenium was significantly greater in women than in men, and that the percentage by which the average width of the splenium was greater than that of the adjacent corpus callosum was significantly greater in females than in males. However, sex differences in bulbosity did not reach significance in children (aged 2-16 yr). In contrast, among the area measurements of the corpus callosum and 22 subdivisions, only 1 exhibited a significant sex difference, which would be expected by chance. The area of the corpora callosa increased significantly with age in children and decreased significantly with age in adults. In adults, the midsagittal surface area of the cerebral cortex decreased significantly with age in women but not in men. These anatomical sex differences could, in part, underlie gender-related differences in behavior and neuropsychological function.