A model of contrast discrimination performance in human observers is developed and then extended to cover effects on performance of anticholinergic drugs. It is shown that it is necessary to assume that neural noise increases at high spatial frequencies in order to provide a satisfactory model of variations in discrimination performance with spatial frequency. The model results are compared with the results of empirical studies in which the effects of the muscarinic antagonist scopolamine (hyoscine) on contrast discrimination performance in human observers are examined. The purpose of the pharmacological work is to test the hypothesis that the differential contrast gain found psychophysically at different spatial frequencies might reflect differential facilitation by extrinsic cholinergic neurons. Contrast discrimination and contrast increment detection are found to be impaired by scopolamine in a manner that depends on both spatial frequency and base contrast. By comparing the empirical data with the predictions of the model, it is concluded that contrast constancy may reflect differential cholinergic modulation.