Receiver operating characteristic analysis has evolved as a useful method for evaluating the discriminatory capability and efficacy of visualization. The ability of such analysis to account for the variance in decision criteria of multiple observers, multiple reading, and a wide range of difficulty in detection among case studies makes ROC especially useful for interpreting the results of a viewing experiment. We are currently using ROC analysis to evaluate the effectiveness of using fused multispectral, or complementary multimodality imaging data in the diagnostic process. The use of multispectral image recordings, gathered from multiple imaging modalities, to provide advanced image visualization and quantization capabilities in evaluating medical images is an important challenge facing medical imaging scientists. Such capabilities would potentially significantly enhance the ability of clinicians to extract scientific and diagnostic information from images. a first step in the effective use of multispectral information is the spatial registration of complementary image datasets so that a point-to-point correspondence exists between them. We are developing a paradigm of measuring the accuracy of existing image registration techniques which includes the ability to relate quantitative measurements, taken from the images themselves, to the decisions made by observers about the state of registration (SOR) of the 3D images. We have used ROC analysis to evaluate the ability of observers to discriminate between correctly registered and incorrectly registered multimodality fused images. We believe this experience is original and represents the first time that ROC analysis has been used to evaluate registered/fused images. We have simulated low-resolution and high-resolution images from real patient MR images of the brain, and fused them with the original MR to produce colorwash superposition images whose exact SOR is known. We have also attempted to extend this analysis to real patient data, using magnetic resonance and single photon emission computed tomography 3D images whose SOR is estimated, but not known exactly. Results suggest that ROC analysis is useful for evaluating observer performance in detecting misregistration when viewing three orthogonal phases of colorwash superposition images, and that these results can be related to image measurements.