Background: Invasion of host cells by Cryptosporidium parvum results in an endoplasmic reticulum (ER) stress response. Results: Host cell calreticulin, GRP78/BiP, Nrf2, and spermidine/spermine N 1 -acetyltransferase increase, whereas poly(ADPribose) polymerase decreases. Conclusion: C. parvum causes an ER stress response culminating in the synthesis of N 1 -acetylspermine by infected cells. Significance: Host ER stress provides a source of polyamines for C. parvum, which lacks ornithine decarboxylase.