We report the development and validation of an osteoporosis-targeted quality of life questionnaire to measure the impact of the disease in the general population. From multiple focus groups with women with osteoporosis, healthy women at risk for osteoporosis, spouses and relatives of women with osteoporosis, and health care providers, we identified over 300 potential items related to the disease. A lengthy questionnaire incorporated these items and was administered to a second large study cohort of 222 women with clinical osteoporosis (history of fracture, significant height loss, and/or kyphosis); 101 women with known low bone mineral density levels that would categorize them as osteoporotic but who had not yet shown obvious physical manifestations of the disease; and 142 women with other conditions (such as arthritis, cancer, depression) expected to also have an impact on quality of life. Final items from among the original 300 were chosen for their demonstrated relationship with osteoporosis as measured by clinical manifestations and low bone density and with quality of life measured by a standard generic questionnaire, the SF-36. The final questionnaire contains 26 scored items in three domains-physical activity, adaptations, and fears- and six nonscored questions relating to osteoporotic changes and diagnosis. This instrument is unique among osteoporosis-targeted questionnaires in that it attempts to measure the total impact of the disease on quality of life within a population at a single point in time.