Two-dimensional (2-D) cranial ultrasound (US) is the principal method for the detection of cerebral injury in the newborn. The aim of this study was to compare 2-D sonographic methods with more advanced 3-D magnetic resonance imaging (MRI) for assessing brain structure. From July 1998 to November 2000, we conducted a prospective methodological study comparing 2-D cranial sonographic measurements with volumes of cerebrospinal fluid (CSF), white matter, grey matter and total volume of brain obtained using 3-D MRI. The study group comprised 63 infants (33 boys), mean gestational age 28 weeks (range 23 to 33 weeks), with imaging studies within 15 days of term equivalent. The highest correlations were between the occipital horn length and total brain volume (R2 = 0.30), the subarachnoid space and both CSF volume (R2 = 0.46) and relative intracranial space occupied by brain tissue (R2 = 0.48). Only 8 (30%) of the 2-D cranial US measures demonstrated good reproducibility. 2-D sonographic measures are limited in reflecting variations in overall cerebral structure, although certain measures, such as subarachnoid space and occipital lobe measures, may be useful in better defining cerebral parenchymal and CSF volumes.