The time-course of low and high intensity primary infections with Heligmosomoides polygyrus was monitored in SJL and SWR mice, both of which usually expel worms within 7 weeks of larval administration. Worm expulsion in these strains was not dependent on the intensity of infection, with low and high intensity worm burdens being lost within the same period of time. The ability to expel worms rapidly was inherited in a dominant manner in F1 offspring of SJL or SWR mice mated with C57Bl10 mice; the latter being a strain in which no loss of worms was evident within 10 weeks of infection. However, neither (SJL × C57Bl10)F1 nor (SWR × C57Bl10)F1 mice expelled worms as rapidly as the parental SJL and SWR strains. (SWR × B10G)F1 [H-2q] mice eliminated worms faster than (SWR × C57Bl10)F1 [H-2bq], suggesting that the b haplotype had a moderating influence on the expulsion process. In fact (SWR × B10G)F1 mice showed a significant reduction in worm burdens by week 4 but by weeks 6–8 the rate of worm loss had slowed considerably. In contrast, SJL and SWR mice, whilst initiating rejection slightly later, (after week 4) expelled all worms within the following 2 weeks. Thus two distinct patterns of response were observed among the fast responder strains as exemplified by SWR and SJL mice on the one hand and (SWR × B10G)F1 on the other. Our results support the hypothesis that the course of a primary infection with H. polygyrus is influenced by multiple host gene loci, some of which are encoded within the MHC. SJL and SWR mice probably have similar if not identical gene combinations at loci which determine a fast responder phenotype, distinguishing them from the other mouse strains which have been studied.