The effects of four different treatment schedules on serum lipid concentrations were studied for 1 year in 402 postmenopausal women in the Kuopio Osteoporosis Study. The women were randomized to four treatment groups: A, Sequential combination of estradiol valerate and cyproterone acetate (Climen); B, Vitamin D3, 300 IU/day; C, Climen+Vitamin D3, D, placebo. In group A, serum concentrations of total cholesterol (Chol) decreased by 4.8% in 6 months and by 6.2% in 12 months (P < 0.001), but in group C the decrease was only 2.9% in 6 months (P < 0.05) and 3.4% in 12 months (P < 0.01). The decline of total-Chol in group A was accounted for by the 6.8% to 7.5% decrease in LDL-Chol levels (P < 0.001). The decrease of LDL-Chol in group C was statistically non-significant. Use of vitamin D3 (group B), increased serum Chol by 2.7% (6 months), P < 0.05 and by 2.1% (12 months) and the increases were the result of the 6.0% to 6.2% increase in LDL-Chol levels in 6 and 12 months, respectively (P < 0.001). Serum concentrations of HDL-Chol and TG remained relatively stable in all groups. No correlations were found between LDL-Chol, 25-OH-D3 and 1,25(OH)2-D3 levels in group B. Our results confirm the beneficial effect of estradiol valerate and cyproterone acetate on the lipid profile. In contrast, vitamin D3 had a negative influence on this profile by increasing serum concentrations of LDL-Chol.(ABSTRACT TRUNCATED AT 250 WORDS)