We have characterized homologous DNA recombination activity in nuclear protein extracts prepared from quiescent and regenerating rat livers. Activity measured in regenerating liver extracts was elevated approximately 35-fold above control, and its appearance closely mirrored the first wave of DNA synthesis, peaking 24 hours after a regenerative stimulus, and returning fairly rapidly to basal levels. We also identified a strand-transferase protein of approximately 100 kDa whose presence in these extracts correlates with homologous recombination activity. Recent evidence suggests that mammalian somatic cells possess a recombinational DNA repair mechanism analogous to that described in the yeast Saccharomyces cerevisiae. Our results indicate that this recombinational repair process may be regulated in vivo by, or play a role in, progression through the cell division cycle.