We examined the effect of total trophozoite homogenates from four axenized strains ofEntamoeba histolytica (HK9, HM1, HM2, and HM3) on the DNA synthesis of subconfluent cultures of Chinese hamster ovary (CHO) cells incubated at low (0.1%) serum concentration. HM1, HM2, and HM3 extracts increased [³H]thymidine incorporation to acidinsoluble material in CHO cells up to a maximum of 2.5, 1.5, and 1.5 times respectively, at doses of amebal protein ranging from 16 to 125 g/ml. HM1 and HM2 extracts at doses higher than those causing maximal stimulation, and HM3 and HK9 extracts above 250 g protein per ml, progressively inhibited [³H]thymidine incorporation by CHO cells at a strain-specific rate. The extracts with both the most potent stimulatory and inhibitory effects were those from HM1 and HM2, also the most virulent strains. This strain-specific ability of amebal products to modulate cell DNA synthesis may play a significant role in amebal virulence.