Tamoxifen (TAM) and estrogen increase serum triglyceride (TG) levels, sometimes inducing severe hypertriglyceridemia and possibly contributing to death. Decreasing the dose of estrogen in estrogen replacement therapy may minimize its adverse effects, including the hypertriglyceridemia. The serum TG, total cholesterol, low-density-lipoprotein (LDL) cholesterol and high-density-lipoprotein (HDL) cholesterol were measured periodically in 116 breast cancer patients on adjuvant TAM therapy at a dose of 10 mg twice daily. The serum TG level was significantly increased 15 months after treatment, but the magnitude of increase was clinically insignificant in most patients (n = 102). If TG levels rose above 400 mg/dl, the dose of TAM was reduced to 10 mg once daily (n =14). The TG was lowered to a safer level after the dose reduction of TAM in 10 of 14 patients. The other four patients had early onset hypertriglyceridemia after beginning TAM (within 6 months), and their TG levels did not decrease satisfactorily after dose reduction. Hence, they required antilipemic medication with or without discontinuing TAM. This study suggests that reducing TAM from 10 mg twice daily to 10 mg once daily decreases the marked hypertriglyceridemia that occurs in some patients during TAM treatment.