The effect of Lps locus and IL-6 on the production of SU (previously termed gp70), a mouse endogenous retroviral gene product, was studied. Back-cross studies using the progeny between (NZB x C3H/HeJ)F1 and C3H/HeJ mice indicate that the basal level of SU is not associated with the Lps locus on chromosome 4. Lipopolysaccharide (LPS) mitogen response-negative mice did not show the enhancement of serum SU production after LPS injection. Spleen cells from LPS-mitogen response-positive but not from negative mice showed increase of IL-6 synthesis in the presence of LPS. Since IL-6 may be involved in the production of serum SU, we tested the effect of IL-6 in a primary hepatocyte culture system. SU production was clearly enhanced in the presence of recombinant IL-6, indicating that IL-6 induced by LPS can enhance the expression of retroviral genome.