Liver cell regeneration after selective zonal injury induced by bromobenzene (acinar zone III damage) and allyl alcohol (acinar zone I damage) was examined in the context of the simple liver acinus. The zonal distribution of necrosis and inflammation was assessed by light microscopy and the volume fraction of necrosis was quantitated at the times of maximal damage. The acinar distribution of hepatocytic [6-3H]thymidine incorporation was determined autoradiographically at 24, 36, 48, 60, 72, and 96 hr after the administration of the toxicants. The mitotic index for each acinar zone was calculated at the time of peak thymidine incorporation after each drug and then at 12-hr intervals for the next 24 hr. Autoradiographic data indicated that the relative contributions of acinar zones II and III to [6-3H]thymidine incorporation were greater after zone III damage (bromobenze), whereas the relative contribution of acinar zone I was greater after allyl alcohol (zone I) damage. This was observed despite the greater degree of damage seem after bromobenzene than after allyl alcohol (volume fractions of necrosis were 26.4 and 10.1%, respectively). Moreover, the acinar distribution of mitosis indicated an increased centrizonal mitosis after centrizonal damage, and an increased periportal mitosis after periportal damage. Thus, the contribution of each acinar zone to liver cell regeneration depends on the acinar location of damage.