Development of a congenic BALB/c mouse strain that contains a segment of chromosome 4 including the Lps(d) allele of the lipopolysaccharide (LPS)-hyporesponsive C3H/HeJ strain is presented. On the basis of LPS-induced spleen cell mitogenesis, macrophage tumor necrosis factor secretion, and tyrosine-phosphorylation in vitro and lethality in galactosamine-sensitized mice in vivo, the C.C3H-Lps(d) strain provides a model of LPS hyporesponsiveness that is comparable to that of the parental C3H/HeJ strain. Analysis of markers in this region indicates that length of the donor fragment is similar to 5.5 centimorgans. Thus, the C.C3H-Lps(d) strain provides an important genetic tool for analysis of markers in this region and for examining functional effects of Lps(d) expression on the BALB/c background.