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To study the short-term effect of unopposed oestradiol (E₂) and sequentially combined hormone replacement therapy (E₂ + P) on C-reactive protein (CRP) in healthy postmenopausal women. Prospective, randomised, placebo-controlled 12-week study. Sixty healthy, normotensive, non-hysterectomised postmenopausal women received either placebo (N = 16) or daily 2 mg micronised oestradiol, either unopposed (N = 16, E₂ group) or sequentially combined with a progestagen on 14 days of each cycle (N = 28, E₂+P group). Data were collected at baseline and at 4 and 12 weeks. CRP levels increased significantly during the 12 weeks in the E₂ and the E₂+P groups compared to placebo. No differences were found between the E₂ group and the E₂+P group [E₂ and E₂+P group together (N = 44) versus placebo: P = 0.01; E₂ versus E₂+P: P = 0.75]. To give a quantitative estimate of the …