A study was conducted to determine the isolated, single-cell detection characteristics of human observers as this information relates to cervical cancer screening. Two interrelated experiments were performed. First, the receiver operating characteristic (ROC) was obtained for slide screening. In this experiment, approximately 1,200 slides were examined. Second, ROCs were obtained for human observer cell discrimination, using a rating method. An individual's curves were computed, assuming a multiple decision criterion. In this experiment, 6,375 cells from the same specimens used in the slide screening experiment were studied. In both experiments, results were analyzed using a Gaussian signal-detection model. This approach provided analytical detection criteria and rigorous definition of ROCs. These experiments addressed the problem of where the screening information lies: (1) in individual cells alone or (2) with additional components in global or other a priori information. We quantified the detection requirements of (1) the Papanicolaou smear screening process, Az = 0.99, and (2) the capabilities of trained cytotechnologists on isolated single cells, Az = 0.87. System modeling using intermediate cell detection instead of "rare event" detection resulted in a reduction of the predicted number of cells required for analysis from approximately 60,000 to 750.