Although IgG with reduced content of galactose has been implicated as important in the autoimmune rheumatoid factor (RF) response in rheumatoid arthritis (RA), relatively little is known about the temporal relationship between RF and the degree of galactosylation of IgG in vivo. We established an experimental model for studying the dynamic association between changes in the relative extent of galactosylation of IgG antigen(s) and the main parameters of RF activity, such as the titer, specificity and functional affinity/avidity. Rabbits hyperimmunized with BSA were used for examining the influence of long-term antigenic stimulation on the galactosylation status of IgG and rheumatoid factor production. The results showed that the galactosylation profile of IgG varied during the humoral anti-BSA response in rabbits and that the accompanying RF response fluctuated in titer and binding avidity for differently galactosylated IgG. The immune complexes (IC) were found to be composed of differently galactosylated IgG differing in capacity to inhibit the agglutination activity of RF. Moreover, the ability of circulating RF to react avidly with rather small IC was associated with a lower content of galactose in complexed IgG. The results suggest that a certain dynamic relationship exists between the oligosaccharide moiety of IgG and the titer and avidity of RF during the normal anti-BSA response of rabbits.