DNA topoisomerase II (topo II) is the target of several clinically useful anticancer drugs. Several of these agents, such as doxorubicin and etoposide (VP-16), are used to treat non-Hodgkin's lymphomas (NHL). To understand the therapeutic selectivity of these drugs, a series of 33 cases of NHL for topo II were analyzed using an immunohistochemical technique that detects the enzyme in formalin-fixed, paraffin-embedded tissue. The average topo II index of high grade (Working Formulation) NHL was 48.6 with a range from 24.4 to 79.7. The average topo II index of low grade (Working Formulation) NHL was 4.4 with a range from 0.9 to 11.2. These two values are statistically different (P < .01). The intermediate grade (Working Formulation) NHL are a heterogeneous group based on topo II staining. The average topo II index value for the intermediate grade neoplasms was 26.7 with a range from 1.4 to 54.9. Because the proliferation marker Ki-67 has been shown to be of prognostic importance when used in the analysis of NHL, 27 cases for also were analyzed for MIB1 (Ki-67). The average MIB1 index of the high grade NHL was 59.8 with a range from 40.7 to 80.3. This average is statistically different (P < .01) than the average MIB1 index of 11.2 (range 1.7-28.3) found in the low grade NHL. Similar to results with topo II, the intermediate grade NHL was a heterogeneous group of tumors with respect to MIBI staining and had an average MIB1 index of 49.1 with a range from 8.9 to 86.7. These results show that high grade NHL have topo II and MIB1 indices that are significantly higher than low grade NHL. Intermediate NHL are more heterogeneous and have topo II and MIB1 indices that range from low to high.