The susceptibility and resistance of inbred mice to Giardia muris was studied during the acute and elimination phases of infection. The infection in susceptible A/J and C3H/He mice was characterized by a short latent period, high cyst output during the acute phase of infection, and prolonged periods of cyst release. In contrast, resistant B10.A and DBA/2 mice had a longer latent period, a lower cyst output during the acute phase, and relatively rapid resolution of infection. The trait of susceptibility and resistance during both acute and elimination phases of the infection was found to be under complex multigenic control as determined by examination of the response of F1 hybrid mice and backcross analyses. The genes controlling this trait did not appear to be linked to the H-2 locus. In addition, the control of the response of mice to G. muris during the acute phase of infection was probably mediated by mechanisms independent from those controlling the response during the elimination phase of infection.