We assessed the mucosal response of previously infected hamsters to low-dose challenge with the hookworm, Ancylostoma ceylanicum. Hamsters were assigned to five treatment groups (Groups 1-5, respectively): naïve, controls; uninterrupted primary infection from day 0; infected, but treated with anthelmintic on day 35 p.i.; challenge control group given only the second infection on day 63; infected initially, cleared of worms and then challenged. Animals were culled on days 73 and 94 (10 and 31 days after challenge), but additional animals were culled from Group 5 on days 80 and 87. The results showed that villus height declined markedly and progressively over time after challenge in Group 5, whilst depth of the Crypts of Lieberkühn and number of mitotic figures in the crypts increased. Mucosal mast cell numbers were only marginally higher than those in naïve controls and not as high as those in mice with uninterrupted infections. Goblet cell counts showed a major increase, as did eosinophils in relation to naïve controls. Paneth cells were also elevated, but did not change over the course of the experiment. The results also drew attention to the tremendous resilience of hookworms, some adult worms surviving throughout, despite highly inflamed intestines.