As part of a cohort study of 150 patients with systemic lupus erythematosus (SLE), we investigated the validity and reliability of several indices of lupus activity, including the UCSF/JHU Lupus Activity Index (LAI), the SLE Disease Activity Index (SLEDAI), and a simple Core Index combining common elements. Validity was assessed by measuring correlations of these indices at the first cohort visit with the physician's global assessment (PGA) of SLE activity. The correlation of M-LAI (LAI modified so as not to contain PGA) and SLEDAI with PGA was 0.64 (95% CI 0.50, 0.70) and 0.55 (95% CI 0.42, 0.64), respectively. Reliability was assessed in a study of 6 patients seen twice, one week apart, by 9 physicians. The interrater reliability and test-retest reliability was greater for LAI (or M-LAI) than for SLEDAI. The Core Index performed better in its correlation with PGA (R = 0.78), although it contained no treatment data or serologic tests. Its interrater reliability and test-retest reliability were comparable with LAI. We conclude that (1) all indices have high validity; (2) LAI and the Core Index have higher reliability; and (3) these indices can be readily assimilated into routine clinic practice.