Several reports have implicated an association between the development of connective tissue disorders and exposure to silicone in breast implant patients. These connective tissue disorders include local or systemic scleroderma-like syndrome and have been characterized by fibrosis as well as the presence of circulating autoantibodies. Whether silicone does potentiate the development of a scleroderma-like syndrome is still to be defined. The purpose of the present study was to determine the effect of silicone on the tight skin (TSK/+) mouse which develops a scleroderma-like syndrome and on its normal pa/pa TSK/- littermate. Groups of six TSK and five of their normal pa/pa littermates were injected subcutaneously with low molecular weight silicone (LMW-PDMS), high molecular weight silicone gel (HMW-PDMS), incomplete Freunds' adjuvant (IFA) or Hank's balanced salt solution (HBSS) in the dorsal neck area and ventrally in the upper chest region. Serum was obtained prior to and 1 month after injection of silicone, IFA, or control HBSS. Antibody levels to bovine serum albumin (BSA), RNA polymerase (RNAP) and topoisomerase I were determined. Mice were then euthanized and strips of skin from the injection sites as well as samples of kidney and liver were studied histologically. No significant pathological changes were observed in TSK/- mice 1 month following injection with HBSS, LMW-PDMS or HMW-PDMS. Skin samples from TSK/+ mice which received LMW-PDMS showed hyperplasia of the dermis and peri-panniculus carnosus tissue and infiltrates of macrophages containing lipid-like vacuolated materials. Lipid vacuoles were observed throughout the deeper dermis as multiple loculated vacuoles. TSK mice which received HMW-PDMS showed similar thickening of the dermis and the peri-panniculus carnosus connective tissue. There were no significant differences in the histologic characteristics of the silicone-injected TSK/+ mice compared to those that received HBSS or IFA. No detectable changes in the kidney, spleen, or liver samples taken from TSK/+ or TSK/- mice injected with HBSS, IFA or silicone (LMW-PDMS, HMW-PDMS) preparations were noted. Baseline circulating antibody levels to BSA, RNAP and topoisomerase were significantly higher in TSK/+ mice compared to the control TSK/- littermates. Administration of silicone (LMW-PDMS or HMW-PDMS) did not significantly alter circulating antibody levels to BSA, RNAP and topoisomerase in either the TSK/+ or the TSK/- mice. The results of this study indicate that silicone administration does not potentiate the development of the scleroderma-syndrome characterized by skin lesions and presence of circulating antibodies in the TSK/+ model.