The objective of this protocol was to provide a rapid, neurofunctionally relevant alternative to region-drawing or automated gyral/sulcal-based techniques. The Cavalieri method and point counting [e.g. Br. J. Radiol. 73 (2000) 679] were used in conjunction with a previously established parcellation methodology [Arch. Gen. Psychiatry 57 (2000) 761] to estimate the volumes of anatomically defined subfields of the prefrontal cortex (PFC) based on landmarks visible on T(1)-weighted magnetic resonance (MR) images. Ten participants (n=5 healthy adults; n=5 patients) were studied. Regional PFC volume estimates derived from point counting methods were reproducible between raters (Intraclass Correlations (ICC)=0.92-0.95) and repeatable within rater (ICC=0.93-0.99). Predicted coefficients of error for individual volume estimates were less than 5%. This protocol provides an efficient means of calculating unbiased volume estimates of the PFC with predictable precision for use in both cognitive and clinical studies.