To compare the morphologic differences in leukemic cells exposed to a nucleotide synthesis inhibitor and a DNA strand damage inducer, L1210 cells incubated with 1-beta-D-arabinofuranosylcytosine (ara-C) or daunorubicin (DNR) were investigated by time-lapse video microscopy, flow cytometry and transmission electron microscopy. At 1.0 microgram/ml of ara-C, cells could be separated into two populations, with some becoming ballooned and deformed, i.e. irreversibly damaged, and others remaining unchanged, i.e. in a proliferative state. In contrast, at 0.10 microgram/ml of DNR, nearly all cells were remarkably enlarged and did not proliferate during 72 hours of observation. Such morphologic changes induced at clinically achievable concentrations of each agent seemed to reflect their differing mechanisms of action on the synthesis of DNA. The methods described may allow the characterization of antileukemic agents as well as the development of clinical designs for their rational application in leukemia patients.