Stereology was used to measure frontal lobe volume on magnetic resonance imaging (MRI) scans in a multi-observer repeated-measures trial in 17 adults. Prior to measurement, MR image volumes were reoriented into coronal sections perpendicular to the bicommissural plane. Three observers blinded to subject identify repeatedly used fixed grid stereology to estimate frontal lobe volumes, defined as all sections of the frontal lobe anterior to the anterior commissure. The lateral ventricles were excluded. Stereological measurement yielded high repeatability and precision, and was time efficient for the raters. The coefficient of error was 0.03. The inter-rater correlation coefficient = 0.95 for three raters; intra-rater correlation coefficients = 0.95-0.98. A comparison was made between stereological and traditional edge tracing measurement of the frontal lobe volumes. The overall correlation between the two methods was 0.95. The use of internal landmarks to define orientation and 3-D orthogonal views to define frontal lobe boundaries on 3-D images was critical to obtaining repeatable measurements. Frontal lobe volumetry by brain MR used to estimate small differences postulated to occur in certain psychiatric and neurologic disorders requires high precision and repeatability. Stereology, a semi-automated method, can reliably estimate frontal lobe volumes. This method may distinguish small frontal lobe volume differences within individuals and between groups.