Abstract Interferons alpha and gamma (IFN-α, IFN-γ) and tumor necrosis factor alpha (TNF-α) exert different regulatory effects on the proliferation and biosynthetic activities of human dermal fibroblasts. Inasmuch as these cytokines bind to specific receptors in order to exert their activities, the expression of IFN-α, IFN-γ and TNF-α receptors on fibroblasts from human adult normal and scleroderma skin cultured in vitro were quantitated. Adsorption was detected by incubating confluent normal and scleroderma fibroblasts with various concentrations of [ 125I]cytokine. Replicate experiments revealed 19,742 ± 2057 ( K d = 1.15 × 10 −9M) TNF-α receptors per normal dermal fibroblast and 15,006 ± 75 ( K d = 6.75 × 10 −10M) TNF-α receptors per scleroderma fibroblast. Cross-linking 125I-TNF-α to its receptor on normal and scleroderma fibroblasts revealed 130- and 100-kDa TNF-receptor complexes. Although no quantitative or qualitative differences were detected between these two cell types with regard to receptor numbers, TNF-α affinity or receptor protein as detected by radiolabelled TNF-α, differences were detected in levels of mRNA specific for TNF-α receptors. Northern blot analysis revealed normal fibroblasts to constitutively contain mainly mRNA specific for the 55-kDa TNF receptor and indicate that they are capable of responding to TNF-α-induced up-regulation of mRNA specific for the 75 kDa TNF receptor. Scleroderma fibroblasts, however, constitutively contain mRNA for both TNF receptors and fail to respond to TNF-α up-regulation of the message for the 75-kDa receptor for TNF. Normal fibroblasts expressed 3320 ± 1781 IFN-α2a and 17,563 ± 1575 IFN-γ receptors with scleroderma fibroblasts expressing 3076 and 16,316 IFN-α2a and IFN-γ receptors, respectively.