Adriamycin was a potent mutagen at the tk locus of L5178Y/TK+/- -3.7.2C mouse lymphoma cells. A dose of 5 ng/ml gave total mutant frequencies of 417/ten to the 6th power survivors (background = 110/ten to the 6th power; survival = 62%) and 350/ten to the 6th power survivors (background = 54/ten to the 6th power; survival = 64%) in the two experiments. The dose was also clastogenic, producing 23 aberrations/100 cells (background = 3/100) (Table 1). The highest dose analyzed for aberration induction (11 ng/ml) gave 105 aberrations/100 cells, with the concurrently treated culture showing a mutant frequency of 1,032/ten to the 6th power survivors (background = 110/ ten to the 6th power). Adriamycin was selected for these studies because it was known to induce a low mutant frequency at the hprt locus, but yet to be a potent clastogen. The authors have recently been evaluating a series of agents that induce low mutant frequencies at the hprt locus, but that are known to be clastogens. These agents, like adriamycin, were clearly mutagenic at the tk locus, induced primarily small colonies, and also induced aberrations in mouse lymphoma cells. These results are consistent with the hypothesis that the tk locus of mouse lymphoma cells can be used to quantitate both intra- and intergenic mutations.