Microscopic examination of the tissue biopsy is the "gold standard" upon which diagnoses is rendered in surgical pathology. This examination is made via the optical microscope using several levels of magnification. The human eye, although a remarkable instrument for extracting the "gestalt" from imagery of the tissue sections and determining the broad category of disease, does not yield a quantitative description of tissue properties. In previous research we have found that the computerized (robot) microscope is capable of assisting the pathologist significantly in forming determinations from digital micrographs as regards the subtyping of follicular lymphoma. This is significant in that the patient treatment plan depends critically upon the accuracy of the subtype determination. Proper treatment, of course, in turn has a major influence on both the patient's quality of life and length of survival. Our work to date has concentrated on moderate resolution computerized microscopy of follicular center cells (approximately 20,000 per case) covering an area of one or two square millimeters. Typing into small, mixed, and large cell categories has been performed as well as or better by the robot microscope than that done by a panel of expert pathologists. In the proposed research, we intend to expand this work to cover much larger areas of tissue (one to two square centimeters) which would encompass a few million cells in toto. The purpose of so doing is to quantitate the low- resolution pattern from which many benign diseases are differentiated from malignancies. In particular, the research will address the question of color quantitation which has not been addressed in our previous work. The robot microscope employed has automated color switching to cover 550 nm, 620 nm, and 450 nm. In the past, color angle measurements have been found to be useful in distinguishing between the subtle differences which exist in chronic active hepatitis and chronic persistent hepatitis. In the proposed research these color angle measurements will be investigated as possible tools for distinguishing not only low-resolution patterns in follicular lymphomas but also the cellular subtype in diffuse lymphomas. Some preliminary work along these lines is illustrated and appears to be promising.