The strategy for evaluating quality of life in clinical trials is an important and complex issue. By comparing the performance of different quality-of-life measures before and after estrogen replacement therapy, it was shown that disease-specific measures had obvious advantages. Although narrow in applicability to the particular patient group, they were the most responsive measures in detecting small, clinically important changes. In clinical trials more attention should be given to how side effects, which often have important implications with regard to quality-of-life, are recorded.