Intravenous immunoglobulins (IVIg) have been used as an immunomodulatory therapy in a variety of diseases. Several mechanisms of action have been proposed, one of which is interference with the cytokine network. We have investigated the effect of IVIg on the cytotoxicity of human TNF alpha. IVIg was capable of protecting L929 fibroblasts from TNF alpha induced cell death. This effect was not species specific and was mediated by both the Fc and the Fab portion of immunoglobulins. Since the effect was also seen when IVIg was added after the removal of TNF alpha from the culture medium, it seems to be independent of the interaction of TNF alpha with its receptor. We conclude that IVIg either act on some point of the TNF alpha signalling pathway or influence the cell cycle unspecifically. The cytoprotective effect of IVIg potentially could contribute to the beneficial effect described for various diseases.