An abnormal immune response towards the Epstein-Barr virus (EBV) has been documented in patients with rheumatoid arthritis (RA). To investigate whether these findings are due to the transformation event caused by EBV, RA blood mononuclear cells and monocyte-enriched preparations were incubated with two different EBV strains: the transforming virus secreted by the cell line B95-8 and the virus released by the P3HR-1 cell line that is not able to transform due to a small deletion in the U2 region of the virus genome. Immunological response was determined by the production of interleukin-1 (IL-1) and tumor necrosis factor (TNF) using ELISA and bioassay systems. There was a striking difference in cytokine measurements with a strong inhibition of IL-1 and TNF production after incubation with the B95-8 virus, but not the P3HR-1 virus. These data indicate that the disturbed reaction of the immune system towards EBV is either dependent on the full transformation of B cells in RA patients or alternatively due to the secretion of a cytokine inhibitor by the B95-8 cell line.