We recently reported three cases of severe hypertriglyceridemia caused by tamoxifen-treatment after breast cancer surgery. In that report we showed that one of the three patients had apo E3/3 and another had E4/2 phenotype. There are few data about the relationship between apoprotein E phenotype, one of modifiers of lipoprotein metabolism, and tamoxifen induced lipemia. In the present study, we studied apo E phenotype to clarify the relationship between apo E phenotype and the changes in lipids during tamoxifen treatment. Plasma triglyceride levels in apo E3/3 and apo E4/3 were 114 +/- 9 mg/dl and 87 +/- 12 mg/dl, respectively, before tamoxifen treatment, and increased significantly to 191 +/- 35 mg/dl in apo E3/3 and 167 +/- 35 mg/dl in apo E4/3 during tamoxifen treatment. There was no significant difference between apo E3/3 and apo E4/3 in triglyceride levels before and during tamoxifen treatment. Plasma levels of total cholesterol during tamoxifen treatment in both apo E3/3 and apo E4/3 were similar to those before treatment. Our data suggest that the increase in triglyceride during tamoxifen treatment may occur in every type of apo E phenotype.