The inheritance of response phenotype to Heligmosomoides polygyrus was investigated in Fl hybrid progeny of fast and slow responder mouse strains. The fast responses of SJL(H-2s) and SWR(H-2q) mice were mediated by dominant genes complementing each other in Fl hybrids which lost worms earlier and produced faster parasite-specific IgG1 antibody responses than either parent. However, the response of Fl hybrids from crosses of C57BL/10 (B10, H-2b) mice with either SJL or SWR differed from that of the parental strains and from each other: (B10 × SWR)F1 lost worms earlier than SWR whilst (B10 × SJL)F1 lost worms later than SJL mice. The Fl progeny of SJL mice with congenic strains B10.G (H-2q) and B10.S (H-2s) lost worms as quickly as SJL. Therefore, the response phenotype mediated by the genome of SJL mice was unaffected by H-2 heterozygosity (with H-2q) or homozygosity (H-2s) despite heterozygosity with B10 background genes, but was slowed significantly by heterozygosity with H-2b. All hybrids involving heterozygosity with B10, irrespective of MHC haplotype or background, failed to clear worms completely, in each case a proportion of mice harbouring residual worm burdens after loss of worms from parental strains.