Flow cytometric analyses of cellular DNA, RNA, and double-stranded RNA content were performed on lymph nodes and extranodal tissue from 177 patients with non-Hodgkin's lymphoma. With increasing histologic grade, a higher incidence of aneuploidy, higher proliferative activity, and higher total and double-stranded RNA content were found. Despite considerable cytometric heterogeneity within histologic grades and morphologic subdivisions, conformity between cytometric and morphologic classifications was observed in 85% of cases. Among intermediate-grade and high-grade lymphomas, increased proliferative activity and diploidy were associated with more frequent responses to treatment. Thus, nucleic acid-derived parameters relate to morphologic subtypes and permit an objective approach to lymphoma classification based on ploidy, proliferation, and RNA characteristics that also had prognostic implications.