This study developed and evaluated Giardia duodenalis cyst propagation using a dexamethasone immunosuppressed CF-1 mouse model as an alternative to a previously described Mongolian gerbil model. The CF-1 mouse model shed significantly more cysts per animal during a 16-18 h collection period compared to the gerbil (averages: 7.8 × 10 cysts/CF-1 mouse and 2.5 × 10 cysts/gerbil). In addition, the patency period for this model differed from both G. muris in mice and G. duodenalis in gerbils in that cysts were shed continuously for over 20 days. Results further showed that the β-giardin gene sequences from gerbil derived and mouse derived G. duodenalis were identical, after 34 serial passages through the CF-1 mouse model. Overall, the CF-1 mouse model produced higher concentrations of cysts per animal, and were genetically and phenotypically stable based on β-giardin gene sequences.