In certain specific pathogen-free colonies, mice, upon aging, produce autoantibodies (RF) specific for the Fc portion of their IgG. In our colony, 129/Sv mice (H-2bvl; Igh-1a) have 10-20 times higher RF levels than C5BL/6 (h-2b; Igh-1b). In addition, the 129 have mainly IgA anti-IgG2a, and the B6 have mainly IgM anti-IgGl. We analyzed the genetic factors that control these differences. The high RF-producer phenotype of strain 129 was inherited as a recessive trait as indicated by the low RF levels of (129 X B6) F1 mice. About 1 of 4 129 X F1 (129 X B6) backcrosses and 1 of 10 (129 X B6) F2 mice had high RF levels, suggesting the involvement of two recessive genes in the control of this RF production. All F2 mice and all but one backcross with high IgA anti-IgG2a levels were homozygous for the Ihg-1a allele of the 129 mouse. In contrast, the B6-type RF was eight times more frequent in Igh-1bb than in Igh-1ab or Igh-1aa mice. High RF titers of either type were suppressed in Igh-1ab mice.