Assays involving monoclonal rheumatoid factor (mRF) reagents are frequently used for the detection of circulating immune complexes, particularly in the rheumatic diseases. A study has been performed to investigate the interaction of two purified mRF reagents with normal sera, sera and synovial fluid from patients with rheumatic diseases and with heat-aggregated human IgG used as a model of immune complexes. Interaction has been measured by a simple laser nephelometric technique and a sensitive radiolabelled mRF precipitation assay. Both mRF reagents showed little reactivity with normal sera but reacted strongly with many of the pathological specimens. Similarly both mRFs reacted with large molecular sized heat aggregates of IgG while a variable reactivity was found with uncomplexed or monomeric IgG. However in pathological sera, both mRFs reacted predominantly with monomeric IgG and a significant correlation was found between the two reagents. This reactivity with monomeric IgG remained after separation of pathological sera in low pH sucrose gradients suggesting it was not due to the presence of small immune complexes of the classical type. In addition no reactivity was found with either reagent with IgG-RF intermediate complexes. It is concluded that mRF reagents are not specific for IgG containing immune complexes. They also react with monomeric IgG and this reactivity is particularly prominent in certain pathological sera. The possible nature of this reactive monomeric IgG is discussed.