Recently, the combination chemotherapy Novantrone, Oncovin, Velban, Prednisone [NOVP] was developed by The University of Texas M. D. Anderson Cancer Center for treatment of Hodgkin's disease [HD]. Preliminary clinical results show that NOVP is as effective as the traditional Mechlorethamine, Oncovin, Procarbazine, Prednisone [MOPP] regimen in achieving remission, but with fewer side-effects. To determine if NOVP is genotoxic, we studied the induction of chromosome breaks and sister chromatid exchanges [SCEs]in lymphocytes of 42 HD patients both before and during NOVP treatment. Furthermore, in vitro bleomycin treatment was used to unmask potential single-stranded DNA breaks inducted by the therapy. Our results showed that NOVP did not cause elevated levels of chromosome or single-stranded DNA breaks, or SCEs. These results together with previous findings that NOVP caused minimal acute and gonadal toxicities suggest that NOVP is less toxic than MOPP. Therefore, this new regimen shows promise as an effective and minimally toxic regimen for treatment of HD.