We consider detection of a nodule signal profile in noisy images meant to roughly simulate the statistical properties of tomographic image reconstructions in nuclear medicine. The images have two sources of variability arising from quantum noise from the imaging process and anatomical variability in the ensemble of objects being imaged. Both of these sources of variability are simulated by a stationary Gaussian random process. Sample images from this process are generated by filtering white-noise images. Human-observer performance in several signal-known-exactly detection tasks is evaluated through psychophysical studies by using the two-alternative forced-choice method. The tasks considered investigate parameters of the images that influence both the signal profile and pixel-to-pixel correlations in the images. The effect of low-pass filtering is investigated as an approximation to regularization implemented by image-reconstruction algorithms. The relative magnitudes of the quantum and the anatomical variability are investigated as an approximation to the effects of exposure time. Finally, we study the effect of the anatomical correlations in the form of an anatomical slope as an approximation to the effects of different tissue types. Human-observer performance is compared with the performance of a number of model observers computed directly from the ensemble statistics of the images used in the experiments for the purpose of finding predictive models. The model observers investigated include a number of nonprewhitening observers, the Hotelling observer (which is equivalent to the ideal observer for these studies), and six implementations of channelized-Hotelling observers. The human observers demonstrate large effects across the experimental parameters investigated. In the regularization study, performance exhibits a mild peak at intermediate levels of regularization before degrading at higher levels. The exposure-time study shows that human observers are able to detect ever more subtle lesions at increased exposure times. The anatomical slope study shows that human-observer performance degrades as anatomical variability extends into higher spatial frequencies. Of the observers tested, the channelized-Hotelling observers best capture the features of the human data.