Seventeen patients with active rheumatoid arthritis (RA) (group I) and fifteen patients with inactive RA (group II), in addition to ten healthy control subjects were included in the present study. All patients were evaluated clinically and biochemically according to the American College of Rheumatology (ACR) core set measures, and a comparison was set between both groups of patients. Serum levels of interleukin–12 (IL–12) and tumour necrosis factor– (TNF– ) were measured using enzyme linked immunosorbent assay (ELISA) in all patients and control subjects. It was found that there was no significant difference in age, sex, disease duration, degree of disability or physician's and patient's global assessments between both groups of patients (P>0.05), but patients with active RA had significantly higher tender joint score, swollen joint score, visual analogue pain scale, erythrocyte sedimentation rate and C– reactive protein compared to patients with inactive RA (P<0.05). Detectable levels of IL–12 in serum were found in 13 out of 17 (76.5%) active RA patients, 6 out of 15 (40%) inactive RA patients and 1 out of 10 (10%) healthy controls. TNF– was also detected in the serum of 12 out of 17 (70.6%) active RA patients, 7 out of 15 (46.7%) inactive RA patients and 1 out of 10 (10%) healthy controls, with significantly higher detectability and significantly higher mean serum levels of IL–12 and TNF– in patients with active RA compared to patients with inactive RA and healthy controls (P<0.05). However, patients with inactive RA had significantly higher detectability and significantly higher serum levels of IL–12 and TNF– compared to the healthy controls (P<0.05) which may reflect the role of IL–12 and TNF– in the pathogenesis of RA. Serum levels of IL–12 correlated positively with TNF– levels in serum in case of active RA patients (r=0.493) and inactive RA patients (r=0.474). It was concluded that significantly elevated serum levels of IL–12 and TNF– may be associated with clinical and laboratory markers of activity of RA; and measurement of serum IL–12 and TNF– levels could be used for assessment of RA activity. IL–12 and TNF– may play an important role in the pathogenesis and inflammatory activity of RA.