Twenty-eight instruments measuring pain, clinical, functional, and global characteristics were administered to 303 patients in a six-month randomized clinical trial of auranofin and placebo in the treatment of patients with rheumatoid arthritis. The instruments were compared with respect to their responsiveness in detecting a treatment effect, the time involved in administering the instrument, the need for the presence of an interviewer, and ease of administration. The instruments' ability to detect a treatment effect was the deciding characteristic in the clinical, pain, and global categories in choosing the preferred instrument. The counts of tender and swollen joints were found to be the most responsive clinical measures, the 10-cm pain line was the most responsive and the fastest to administer of the pain instruments, and the categorical self-assessment of arthritis was the most responsive global measure. In the functional ability category, the Health Assessment Questionnaire (HAQ), the Keitel Functional Assessment, and the Quality of Well-Being (QWB) Questionnaire were equally responsive. The HAQ was the shortest and the only self-administered questionnaire. The QWB has had the most extensive validation work but was a complex instrument requiring intensive interviewer training. The Keitel was the most time-consuming instrument, but had the advantage of high interobserver agreement. The design of future trials can be guided by the information obtained in this study on their relative efficiencies and ease of use.