Tumor necrosis factor-alpha (TNF) is a major cytotoxic monokine with wide spectrum of biologic effects. Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease of unknown etiology. Abnormalities of T lymphocytes with hyperactivated B lymphocytes, and formation of immune complexes and autoantibodies are the hallmark of the disease. TNF among other cytokines has been suggested to play an important role in the immune dysregulation observed in SLE patients. Systemic Sclerosis (SSc) is a generalized disorder of connective tissue characterized clinically by thickening and fibrosis of the skin (scleroderma) and by distinctive forms of involvement of internal organs. A diverse array of fibrogenic cytokines among which TNFa is released and may be capable of inducing or modulating the scleroderma fibroblast phenotype through mediating irreversible alterations in connective tissue inducing fibrosis of multiple organs that characterize the disease, thus sharing in its pathogenesis. High levels of sTNF have been reported in several autoimmune diseases, and may be implicated in the etiopathogenesis of these two autoimmune diseases as well as others. The objective of this study was to measure serum level of tumour necrosis factor-alpha (TNF) in a group of Egyptian patients with systemic sclerosis (SSc) and another group with systemic lupus erythematosus (SLE), and to correlate it with various parameters of these two diseases. Seventy five subjects were included in the present work, and were classified into three groups: thirty female patients with Systemic Lupus Erythematosus (SLE), thirty female patients with Systemic Sclerosis (SSc), and fifteen healthy female subjects, of matched ages who served as control. Systemic Lupus Activity Measure (SLAM) index was used to assess disease activity in SLE patients. Serum levels of TNF were assessed using EASIA assay. Results showed that the mean sTNF level was significantly higher than the control group in both SLE as well as SSc. The sTNF levels were correlated to SLAM index, and elevated erythrocyte sedimentation rate. Statistically significant differences were observed in SLE patients with lupus nephritis and neuropsychiatric lupus erythematosus than unaffected patients with SLE. Also, statistically significant differences were observed in SSc patients with esophageal disease and interstitial pulmonary disease than unaffected SSc patients. In conclusion, sTNF level is increased in SLE as well as SSc patients. It correlates significantly with various disease parameters. Our findings suggest that estimation of circulating sTNF may be of value in detection and evaluation of an ongoing inflammatory disorder, and may also provide novel approaches for controlling these autoimmune diseases.