Objective. To investigate whether agonist antiplatelet-derived growth factor receptor ␣ (anti-PDGFR␣) antibodies are present in the serum of patients with systemic sclerosis (SSc; scleroderma).Methods. Sera were obtained from healthy subjects and scleroderma patients. An electrochemiluminescence binding assay was performed for detection of serum autoantibodies to PDGFR␣, PDGFR␤, epidermal growth factor receptor (EGFR), and colonystimulating factor receptor 1 (CSFR1). Serum immunoglobulin was purified by protein A/G chromatography. To assess Ig agonist activity, PDGFR␣-expressing cells were incubated with pure Ig and the level of receptor phosphorylation determined in an enzyme-linked immunoassay, as well as by Western blotting. Ig agonist activity was also assessed in a mitogenic assay and by MAP kinase activation in a PDGFR␣-expressing cell line.Results. Sera from 34.3% of the healthy subjects and 32.7% of the SSc patients contained detectable autoantibodies to PDGFR␣ and PDGFR␤, but not EGFR or CSFR1. Purified Ig from these sera was shown to retain PDGFR binding activity and, at 200-1,000 g/ml, exhibited no agonist activity in a cell-based PDGFR␣ phosphorylation assay and did not stimulate a mitogenic response or MAP kinase activation in a PDGFR␣-expressing cell line. Two purified Ig samples that were unable to bind PDGFR␣ did exhibit binding activity to a nonglycosylated form of PDGFR␣.Conclusion. Although approximately one-third of sera from scleroderma patients contained detectable autoantibodies to PDGFR, these antibodies were not specific to scleroderma, since they were also detected in a similar percentage of samples from normal subjects. PDGFR␣ agonist activity was not demonstrated when purified Ig from these sera was tested in cell-based assays.