Previous reports have shown that deficient galactosylation of serum IgG occurs in patients with rheumatoid arthritis (RA) and other autoimmune disorders. In this study, we investigated the relationship between galactosylation of serum IgG and disease status in a population of Pima and Papago Indians, who are characterized by a frequent occurrence of RA. The mean galactose levels of serum IgG collected from 11 individuals 1.5-10 years prior to onset (T1), at onset (T2), and 1.7-7 years post-onset (T3) of RA were lower than those from 25 seronegative controls without RA from the same population (P=0.01, 0.005, and ≦0.001, respectively). The mean galactose content of IgG decreased in the order T1>T2>T3, but the differences were not significant. The galactosylation of serum IgG from the RA patients did not differ from that of seropositive Pima Indian controls who did not develop RA over the course of study. The occurrence of IgG galactose deficiency in individuals with RA prior to the onset of the disease supports the contention that this phenomenon may be a risk factor for the development of RA. Furthermore, the occurrence of IgG galactose deficiency in healthy seropositive individuals suggests a relationship between diminished galactosylation and induction of rheumatoid factor (RF). © 1994 Springer-Verlag.