Previous work has shown that chlordecone (CD)-amplified CCl4 hepatoxicity and lethality can be mitigated by pretreatment with (+)-cyanidanol. These studies also revealed that stimulated hepatocellular regeneration might play an important role in the cyanidanol protection of CD-amplified CCl4 toxicity. The present studies conducted over a time course of 0 to 120 hr after CCl4 challenge describe sequential changes in hepatic (3)H-thymidine incorporation into hepatocellular nuclear DNA, polyamines and related enzymes, and histomorphometry of liver sections from variously treated rats. Male Sprague-Dawley rats (125-150 g) were maintained on a control diet or on a diet contaminated with CD (10 ppm for 15 days) and/or pretreated with cyanidanol (250 mg/kg, ip) at 48, 24 and 2 hr before a single ip injection of 50 microliter CCl4/kg(L) to 100 microliter CCl4/kg(H) on day 16 of the dietary protocol. Cyanidanol-stimulated (3)H-thymidine incorporation was highly suppressed in rats receiving the CD + CCl4(H) combination treatment up to 36 hr, but after this time point a marked increase was observed. Hepatocellular regeneration, quantified histomorphometrically as volume density of cells in metaphase was progressively increased in rats protected from CD + CCl4 interaction by cyanidanol, starting at 36 hr and lasting until 72 hr.