Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs. It has been demonstrated that serum prolactin levels are increased in patients with various connective tissue diseases. The aim of this study was to investigate the possible source of excessive prolactin synthesis in SSc and its effects on immune cells. The study group consisted of 52 patients with diffuse SSc (44 women and eight men) and 52 age and sex matched healthy controls. The methods used were: ELISA and indirect immunofluorescence. Our results show significantly elevated level of prolactin in male and female patients with SSc and increased prolactin production by SSc lymphocytes as compared to healthy donors X lymphocytes (25.4+/-11.0 vs. 13.4+/-5.0 absorbance units). Patients X and healthy controls X lymphocytes, showed equal presence of prolactin receptors. Soluble interleukin 2 receptor (CD25) concentration, was significantly higher in supernatants of prolactin stimulated lymphocytes, as compared to non-stimulated lymphocytes. We conclude that lymphocytes might contribute to elevated prolactin levels in patients with SSc and that these cells themselves may be sensitive to prolactin stimulation. Therefore, a pharmacologic attempt to lower prolactin levels in patients with SSc could proof beneficial.