Cq3 was identified in C57BL/6J (B6) × KK-A^y F₂ mice as a quantitative trait locus (QTL) that controls plasma cholesterol and phospholipid levels, and normolipidemic B6 allele was associated with increased lipids. Cq3 was statistically significant in F₂-a/a, but not in F₂-A^y/a; probably because the Cq3 effect was obscured by introduction of the A^y allele, which in itself has a strong hyperlipidemic effect. Because the peak LOD score for Cq3 was identified near D3Mit102 (49.7 cM) on chromosome 3, linkage analyses with microsatellite markers located at 49.7 cM were performed in KK × RR F₂, B6 × RR F₂, and KK × CF1 F₂. However, even a suggestive QTL was not identified in any of the three F₂. By testing all pairs of marker loci, I found a significant interaction between Cq3 and the Apoa2 locus, and F₂ mice with the Apoa2^KK/Apoa2^KK; D3Mit102^B6/D3Mit102^B6 genotype had significantly higher cholesterol levels than did F₂ mice with other genotypes. The results showed that the `round-robin' strategy was not always applicable to the search for QTL genes; probably because specific gene-to-gene interaction limited the validity of the strategy to the utmost extent.