Objective: To investigate the effect of a low dose of fluoride, combined with hormone replacement therapy (HRT) or alone, on serum lipids and lipoproteins in postmenopause. Study design: One hundred and thirty-five healthy postmenopausal women were enrolled in this prospective study and randomly assigned to: (1) oral monofluorophosphate (MFP, 25mg per day); or (2) HRT (a combination of oral conjugated estrogen 0.625mg in conjunction with medroxyprogesterone acetate 5mg daily); or (3) HRT+MFP; or (4) placebo, for 18 months. Serum lipid and lipoprotein levels were measured at enrollment and at the end of the study period. Results: Total cholesterol was not significantly different among groups, with a decrease in the HRT and the HRT+MFP groups (respectively, -7.8 and -7.9%), and a small increase in the MFP group (0.4%). LDL-C did not differ significantly in the groups, with a decrease in the HRT and HRT+MFP groups (respectively, -10.3 and -10.4%), and a slight increase in the MFP group (0.8%). TG decreased with -12 and 11.8% in the HRT and HRT+MFP groups (P=0.052 and 0.055, respectively), but a slight increase was seen in the MFP group (1.4%). For HDL-C, both HRT and HRT+MFP groups showed a small increase (respectively, 3.5 and 3.6%), whereas MFP group showed a slight decrease (-0.9%, NS). Conclusion: We conclude that long-term use of a low dose of fluoride had no significant adverse changes in the lipid and lipoprotein profile in postmenopause. It neither attenuated nor potentiated the effect of HRT on lipids and lipoproteins.