A patient with a malignant peripheral nerve sheath tumor (MPNST) was treated with IVIg for multiple sclerosis. Her MPNST course was remarkably longer and more indolent than expected; she achieved a disease-free interval (DFI) of 30 months. Seven other patients, who were not treated by IVIg, had a relatively aggressive course (median DFI 3 months). These results led us to examine the effect of IVIg on the growth of sarcoma in vitro and in vivo in an experimental model of MCA-bearing mice. When added to MCA-105 sarcoma cell cultures, IVIg produced a dose-dependent inhibitory effect on [(3)H]-thymidine incorporation. The maximal inhibitory effect was at a concentration of 50 mg/ml IVIg. Cell cycle analysis revealed a hypodiploid peak at the lower fluorescence values which appeared in the samples treated with IVIg. These results demonstrate that the anti-proliferative activity results from an apoptotic effect of IVIg on the tumor cells. In a second set of experiments, we evaluated the capability of IVIg, when administered orally or subcutaneously, to inhibit the growth of MCA-105 sarcoma lung metastases. A decrease in the mean lung weight was observed in the mice that were treated by s.c. or oral administration, the latter being more effective. A possible role for IVIg in the treatment of MPNST and other soft tissue sarcomas is suggested.