Noise properties of active matrix, flat-panel imagers under conditions relevant to diagnostic radiology are investigated. These studies focus on imagers based upon arrays with pixels incorporating a discrete photodiode coupled to a thin-film transistor, both fabricated from hydrogenated amorphous silicon. These optically sensitive arrays are operated with an overlying x-ray converter to allow indirect detection of incident x rays. External electronics, including gate driver circuits and preamplification circuits, are also required to operate the arrays. A theoretical model describing the signal and noise transfer properties of the imagers under conditions relevant to diagnostic radiography, fluoroscopy, and mammography is developed. This frequency-dependent model is based upon a cascaded systems analysis wherein the imager is conceptually divided into a series of stages having intrinsic gain and spreading properties. Predictions from the model are compared with x-ray sensitivity and noise measurements obtained from individual pixels from an imager with a pixel format of 1536 x 1920 pixels at a pixel pitch of 127 microns. The model is shown to be in excellent agreement with measurements obtained with diagnostic x rays using various phosphor screens. The model is used to explore the potential performance of existing and hypothetical imagers for application in radiography, fluoroscopy, and mammography as a function of exposure, additive noise, and fill factor. These theoretical predictions suggest that imagers of this general design incorporating a CsI: Tl intensifying screen can be optimized to provide detective quantum efficiency (DQE) superior to existing screen-film and storage phosphor systems for general radiography and mammography. For fluoroscopy, the model predicts that with further optimization of a-Si:H imagers, DQE performance approaching that of the best x-ray image intensifier systems may be possible. The results of this analysis suggest strategies for future improvements of this imaging technology.