A 2-armed, masked study was performed on 1,275 AutoCyte PREP (TriPath, Burlington, NC) slides. Manual screening (current practice [CP]) was compared with automated screening with location-guided screening (LGS) using the AutoPap system with the SlideWizard 2 automated review microscopy station (TriPath). Cytologic adjudication determined "truth" for each slide. LGS identified more abnormal cases at all interpretive levels and classified abnormalities more specifically. For high-grade squamous intraepithelial lesions and above, the overall sensitivity of appropriate triage to pathologist review was 98.4% for LGS and 91.1% for CP. The appropriate triage for all abnormal cases was 92.1% for LGS and 87.9% for CP. The potential exists for more accurate and productive cytologic interpretation using this system, which requires no manual screening of a portion of slides and only limited review of another portion of "predotted" slides.