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, 25 mg per day); or (2) HRT (a combination of oral conjugated estrogen 0.625 mg in conjunction with medroxyprogesterone acetate 5 mg 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. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.