The parameters involved in the Disease Activity Score of 28 joints (DAS28) are not mutually independent, and the evaluation excludes ankle and foot joints. We developed a new quantitative and comprehensive assessment of the activity of rheumatoid arthritis (RA), called the handy rheumatoid activity score, with 38 joints (HRAS38), to overcome these disadvantages of DAS28. Forty-six RA patients who recently completed a 1-year infliximab therapy were evaluated for DAS28 (C-reactive protein; CRP) and HRAS38 at 0, 2, 6, 14, 22, 30, 38, 46, and 54 weeks. The 38-joint evaluation in HRAS38 includes 28 joints of DAS28 except for the shoulder joints, with the addition of ankle and metatarsophalangeal joints. The extent of joint swelling was rated on a scale of 0-3. The HRAS38 score is the cumulative sum of three parameters including: (1) a global assessment of disease activity [visual analog scale (VAS) 0-100 mm] by the patient, (2) swollen joint score based on a 38-joint assessment by a physician (0-114), and (3) serum concentration of CRP (mg/l). Scatter plots of HRAS38 and DAS28(CRP), and subsequent linear regression analysis demonstrated a statistically significant correlation between methodologies (r = 0.846, P < 0.0001). Infliximab treatment resulted in a statistically significant (P < 0.001) decrease in the mean HRAS38 score from 130.5 to 56.5 within 2 weeks of treatment and at 52 weeks of therapy scores were still reduced at 52.5. The mean DAS28(CRP) was also significantly (P < 0.001) reduced from a baseline value of 5.8 to 3.7 after 2 weeks treatment with a final value of 3.2 after 52 weeks of therapy. Infliximab reduced the progression of joint destruction by 85%, for terms before infliximab as determined by radiographic analyses. The degree of progression appeared to be associated with the mean HRAS38, although this observation was not shown to be statistically significant by regression analysis (r = 0.307). The HRAS38 score comprises minimal and independently acquired parameters and is an effective and comprehensive measure of disease activity in RA patients.