Prolactin (PRL) has been implicated as an importantin vivomodulator of cellular and humoral immunity. In order to elucidate the impact of elevated serum PRL levels on the immune system, we measured circulating autoantibodies in the serum of 33 hyperprolactinemic (HPRL) women and in 19 healthy women with normal PRL levels. All sera were examined for the presence of autoantibodies against 15 different antigens, including: ssDNA, dsDNA, histones (H2AH2B), Sm, RNP, SS-A/Ro, SS-B/La, cardiolipin, Scl-70, Jo1, collagen, glomerular basement membrane (GBM), pyruvate dehydrogenase (PDH), proteinase-3 (PR3) and MPO. Twenty-five of 33 (75.7%) HPRL women were found to have at least one autoantibody, while none of the 19 women with normal PRL had any. Eight HPRL women had seven or more (up to nine) different autoantibodies. Some of the autoantibodies were more frequently expressed than others, namely: anti-ss-DNA, anti-dsDNA, anti-Sm, anti-PDH and anti-SS-A/Ro. Autoantibodies to the autoantigens tested are common in a variety of autoimmune and rheumatic disorders including systemic lupus erythematosus (SLE), Sjoügren’s syndrome, mixed connective tissue disease (MCTD), scleroderma, primary biliary cirrhosis (PBC), polymyositis/dermatomyositis and vasculitis. Yet none of the HPRL women whose serum was found to contain high titers of autoantibodies presented with symptoms related to the respective autoimmune disorders. Our results support the role of PRL in the regulation of immune responses in man.