Recombinant inbred strains were used to demonstrate the existence of a major locus on chromosome 1, designated Sap, which controls the endogenous concentration of the mouse acute phase reactant, serum amyloid P-component (SAP). Levels of SAP were associated with alleles at the Ly-9 locus in two sets of RI strains: BXD (C57BL/6J x DBA/2) and BXH (C57BL/6J x C3H/HeJ). Low endogenous levels of SAP were present in the C57BL/6J progenitor strain and in most of the RI strains which inherited the Ly-9 b allele. High levels of SAP were present in the DBA/2J and C3H/HeJ progenitors and in most of the RI strains which inherited the Ly-9 a allele. In the B XD strains 91% of the genetic variation of SAP levels was accounted for by segregation at the Ly-9 locus while an additional 9% was attributed to genetic factors unlinked to Ly-9. In the BXH strains the percentage of genetic variation accounted for by Ly-9 segregation was reduced to 46%, while 54% was accounted for by other genetic factors. Because of background genetic variation it was not possible to detect any crossovers between Sap and Ly-9. However, in the BXD strains the linkage between Sap and Ly-9 appears to be quite close. The B6.C-H-25 c congenic strain, which carries a segment of BALB/c chromosome 1 including the minor histocompatibility locus H-25 on a C57BL/6By background, had the same endogenous SAP level as the BALB/c donor strain.