Infection with helminth parasites typically evokes a T helper 2-cell response in the mammalian host. Interleukin (IL)-4 and IL-13 are important in the rapid expulsion of parasitic nematodes, with the absence of either cytokine being compensated for by the other. However, the IL-4 and IL-13 common signaling molecule, signal transducer and activator of transcription 6 (STAT-6) appears to be mandatory for the spontaneous expulsion of enteric helminths. Mice genetically deficient in IL-4, IL-13, or STAT-6 were infected with the cestode Hymenolepis diminuta and worm infectivity and jejunal goblet cell responses assessed 12–18 days postinfection (PI). Only the STAT-6 knockout (KO) animals harbored adult worms; neither gravid adult nor stunted H. diminuta was obtained from the infected IL-4 KO or IL-13 KO mice ≥12 days PI. Also, the establishment of worms in the intestine of STAT-6 KO animals was associated with a reduced goblet cell response. These findings support the hypothesis that increased mucin production is an important part of the host response to tapeworm infection and that functional STAT-6 signaling may be an absolute requirement for the rejection of intestinal cestodes and thus, helminth parasites in general.