In this paper we present a Grid-aware middleware system, called GridPACS, that enables management and analysis of images in a massive scale, leveraging distributed software components coupled with interconnected computation and storage platforms. The need for this infrastructure is driven by the increasing biomedical role played by complex datasets obtained through a variety of imaging modalities. The GridPACS architecture is designed to support a wide range of biomedical applications encountered in basic and clinical research, which make use of large collections of images. Imaging data yields a wealth of metabolic and anatomic information from macroscopic (e.g., radiology) to microscopic (e.g., digitized slides) scale. While this information can significantly improve understanding of disease pathophysiology as well as the noninvasive diagnosis of disease in patients, the need to process, analyze and store large amounts of image data presents a great challenge.