In an open study, self-ratings of bodily symptoms, mood (before and after stress), and cognitive performance were investigated in 25 women (aged 54-66 years) who for approximately 10 years had been taking an oral preparation of hormone replacement therapy (HRT), tibolone (Livial; 2.5 mg/ day). Tibolone has a unique profile, with estrogenic, progestogenic, and androgenic actions. The control group of 25 women had never taken HRT. Each woman in this group was pair-matched to one in the tibolone group on age, years since menopause, IQ, years of secondary education, and occupation. The groups were matched on their anxiety and depression scores on the Hospital Anxiety and Depression rating scale. Exclusion criteria were scores on this scale in the clinical range and any current illness or recent use of psychoactive medication. The women who were taking tibolone felt significantly less clumsy and had less severe palpitations than the control group. After exposure to a mildly stressful test, the control group felt more anxious, but this change was not seen in the group receiving tibolone. The group taking tibolone had significantly better semantic memory (memory for facts), as assessed in a category generation task, but they did not differ in tests of episodic memory (memory for events). An unexpected finding was that the tibolone group performed significantly worse on a sustained attention task and a planning task, tasks that are associated with frontal lobe function. Our results suggest that the effects of HRT on cognition may be influenced by the type of HRT, the duration of treatment, the nature of the tests, and the brain region controlling the cognitive function.