The in vivo induction of chromosome aberrations has been studied in the liver cells of rats exposed to N-nitrosodiethylamine (DEN). Rats were treated with DEN before or after partial hepatectomy. For chromosome analysis, liver cells were isolated by a collagenase digesting procedure. In both treatment schedules, DEN caused significant and dose-dependent chromosome structural aberrations at dose levels as low as 0.5-4.0 mg/kg which are comparable to the range employed in lifetime carcinogenicity tests. Repeated exposures to DEN increased the rates of aberrations. By the procedure described above, detection of clastogenic activities of other hepatocarcinogens will be possible.