Prolonged immunization of rabbits with bovine (BSA) and human (HSA) se
rum albumins resulted not only in the production of antigen specific I
gG but also in the synthesis of rheumatoid factor (RF)-like autoanti-I
gG antibodies in 9 out of 12 animals. RF activity was associated with
19S and 7S fractions of sera. The appearance, duration and disappearan
ce of RF correlated with the presence and duration of circulating immu
ne complexes (CIC). The immunization period was accompanied by fluctua
tions in RF activity and CIC level. This is probably due to the format
ion of secondary IC between RF and still existing CIC as was shown by
analysis of CIC composition in vitro. The results suggest that RF resp
onse in the rabbit may be a composite response based on the contributi
ons of both non-specific and specific effects of immune complexes. Hyp
erimmunized rabbits were shown to be a useful model for studying the c
irculation events concerning the relationship between rheumatoid facto
r and immune complexes.