The purpose of this study was to use structural equation modeling techniques to examine potential interrelationships among psychological factors, immunologic activation, and disease activity in rheumatoid arthritis (RA). The subjects were 80 male patients with a diagnosis of classic or definite RA. Measures included the Beck Depression Inventory, the Arthritis Helplessness Index, and the Arthritis Impact Measurement Scales (AIMS) pain score. Joint counts and immunophenotypic analyses of peripheral blood lymphocytes also were collected. Path analysis showed that percentage of HLA-DR+ cells in the peripheral blood and helplessness were related to join count. In addition, joint count had an effect upon depression. Depression had an effect upon pain, but there was no reciprocal effect of pain upon depression. This study describes a preliminary path model of interrelationships among psychological factors, immunologic activation, and disease activity in RA.