This study was undertaken to determine whether the expression of 17.109, 6B6.6 and 4C9 rheumatoid factor (RF) idiotypes is predictive of the development of rheumatoid arthritis (RA) and whether the RF response is idiotypically restricted in an inbred population of Pima Indians who have a genetic predisposition for the disease. Serial sera were obtained from 25 subjects who developed RA and 25 RF-positive subjects who did not develop RA over the course of a longitudinal community health survey. RF titers and titers of the RF-associated idiotypes 17.109, 6B6.6 and 4C9 were determined by ELISA, and the relationship between 6B6.6 and 4C9 was analyzed by cross-absorption studies. Expression of the three RF-associated idiotypes was found in both the subjects who developed RA and those who did not. The amount of idiotype expressed was variable, but a few subjects in both groups had high levels indicative of an oligoclonal RF response. Reactivity with 6B6.6 and 4C9 antiidiotypes overlapped, with 4C9 appearing to mark a broader spectrum of RF than 6B6.6. Thus, even in an inbred and genetically predisposed population, the RF-associated antiidiotypes studied here did not identify a dominant idiotypic response and were no better markers for the development of RA than was RF itself.