The authors present experimental techniques for the diagnosis of malignant lymphoma and benign lymphocytosis in lymphoid-rich effusions with the use of an inexpensive microcomputer-based video system for computerized interactive morphometry (CIM). Lymphoid cells were randomly selected by a trained observer from real-time images of Papanicolaou-fixed and -stained cytospin smears prepared from pleural, peritoneal, or pericardial effusions. The lymphoid cells were classified by the instrument, based on the size and shape of their nuclear profiles. The morphometric data collected by the instrument were interpreted by a simple rule-based expert system that classified the smears as benign or malignant. One hundred four cases, including 28 malignant lymphomas, 63 benign lymphocytoses, 8 chronic lymphocytic leukemias, and 5 cases with incomplete immunopathologic data, were studied retrospectively. Sixty-three of these effusions had been stained to detect light chain monoclonality. Ninety-one effusions were correctly classified by the expert system. There were four potential false negative diagnoses and one potential false positive diagnosis by the CIM system. Eight effusions from patients with chronic lymphocytic leukemia (CLL) were consistently classified as benign. Although the author's series of patients with a history of CLL is small, their results suggest that CIM is unsuitable for the diagnosis of malignancy in these effusions. If only those effusions from patients with a history of CLL are excluded, the predictive value of a diagnosis of malignant lymphoma was 96.5%, whereas the predictive value of a diagnosis of benign lymphocytosis was 94.0%.