The interaction of 3 monoclonal antibodies (MAbs)--anti-HeFi-1, anti-2H9, and anti-IRac--with Reed-Sternberg (RS) cells was examined in vitro. MAb anti-2H9 induced specific modulation of the corresponding antigen (Ag) from the cell surface. Cell-bound anti-2H9 antibody (Ab)-Ag complexes rapidly disappeared during incubation of cells at 37 degrees C for 2-4 hours. This early loss was followed by reappearance of the Ag on the cell surface within 4-12 hours. In contrast, anti-HeFi-1 and anti-IRac bound avidly to the surface of RS cells and persisted for more than 3 days. During this period, there were no significant changes in the expression of HeFi-1 or IRac Ag on the surface of tumor cells. Cell surface-bound Abs were distributed uniformly, and there was no evidence of microaggregation, as determined by electron microscopy. None of the 3 MAbs was directly cytotoxic or exhibited complement-mediated cytotoxicity. On the basis of these findings (persistence of anti-HeFi-1 and anti-IRac on the cell surface), these 2 MAbs may be suitable for immunoimaging and immunotherapy for Hodgkin's disease.