To investigate the induction of gene amplification by a transient inhibition of DNA synthesis, V79-AP4 Chinese hamster cells were treated with 1-beta-D-arabinofuranosylcytosine (araC). At given intervals after the treatment, the frequency of N-(phosphonacetyl)-L-aspartate (PALA)-resistant colony-forming cells was determined. The data indicate that PALA resistance was enhanced by araC treatment and that this effect was essentially due to the amplification of the CAD gene. Moreover, by analysing the kinetics of induction of PALA resistance it was found that its time course paralleled araC induction of sister chromatid exchanges (SCEs). These results suggest that gene amplification and SCE occur in the same target cells.