The Karnofsky Performance Status Scale (KPS) is widely used to quantify the functional status of cancer patients. However, limited data exist documenting its reliability and validity. The KPS is used in the National Hospice Study (NHS) as both a study eligibility criterion and an outcome measure. As part of intensive training, interviewers were instructed in and tested on guidelines for determining the KPS levels of patients. After 4 months of field experience, interviewers were again tested based on narrative patient descriptions. The interrator reliability of 47 NHS interviewers was found to be 0.97. The construct validity of the KPS was analyzed, and the KPS was found to be strongly related (P less than 0.001) to two other independent measures of patient functioning. Finally, the relationship of the KPS to longevity (r = 0.30) in a population of terminal cancer patients documents its predictive validity. These findings suggest the utility of the KPS as a valuable research tool when employed by trained observers.