The effects of chronic administration of estrogens on the lipid profile in males are not fully understood. We have studied the effect of chronic administration of estrogens on the lipid profile in a group of transsexual (TS) Canarian men who were taking estrogens and anti-androgens for a minimum of 3 years. In this cross-sectional study of cases (n=27) and controls (n=26), plasma lipid profile and selected biochemical and hormonal features were studied. TS subjects had shorter stature than controls, and, after adjusting for height and weight, we found that they had lower values of serum free testosterone (FT) and higher estradiol (E2) levels than controls. The TS group had lower total and low-density lipoprotein (LDL) cholesterol and lower apoprotein B (Apo B) levels than the control group. Biochemistry was similar in both groups. The distribution of estrogen receptor gene polymorphisms (ER-Pvu and ER-Xba) was also similar in both groups. Serum Apo B concentration was related to ER-Xba polymorphism. No other association between lipid profile and the distribution of ER-Pvu and ER-Xba was found. We conclude that the chronic administration of estrogens in men could produce an increase in serum estradiol, a decrease in free testosterone levels, and a reduction in total cholesterol, LDL-cholesterol, and Apo B levels. The ER-Xba polymorphism may influence the Apo B response to exogenous estrogen in males.