A larger premorbid brain is hypothesized to provide neuronal reserve against AD. Using MRI data from ongoing studies of normal aging and AD, the authors tested this hypothesis. Mean total intracranial volume was 15.8 cm(3) smaller for cases among women (n = 121 normal and 104 AD; p = 0.24) and 10.1 cm(3) larger for cases among men (n = 63 normal and 62 AD; p = 0.59). These differences are small and nonsignificant, suggesting that head size per se is not a critical determinant of AD.