Variation in the CD4/non-T autologous mixed lymphocyte reaction (AMLR) with disease activity in juvenile rheumatoid arthritis (JRA) was evaluated by repeated study of 5 patients with rheumatoid factor (RF) negative and 8 patients with seropositive polyarticular onset. Results of repeated studies of adult controls fell within the limits of 1 SD from the previously established normal mean. In contrast, greater variation occurred in results of patients with JRA. Patients with RF negative JRA showed no correlation with disease activity but in seropositive patients stimulation indices in the AMLR improved with a reduction in disease activity and RF titer.