Three studies were conducted to examine parasite resistance and anthelmintic efficacy in the horse. In Experiment 1, 3 fenbendazole (FBZ) treatments (5 mg/kg BW, 10 mg/kg BW, or a larvicidal, 50 mg/kg BW) were administered to horses treated only with FBZ for 18 mo prior. Resistance to FBZ was documented by larval hatch assay and fecal egg count reduction (FECR) tests. In all treatment groups, FECR was not greater than 90%. In Experiment 2, the efficacy of moxidectin (MOX), ivermectin (IVM), and the larvicidal FBZ dose were studied. Mean FECR was 99.91%, 98.73%, and 84.3%, respectively. Animals treated with MOX and IVM had higher (P < 0.05) FECR than the FBZ group. When FECR was analyzed by age, there were no differences among treatment groups in the mature horses, whereas the MOX and IVM groups were higher (P < 0.05) than the FBZ group in the young horses. Experiment 3 determined the efficacy of a year-long quarterly rotation. A farmwide study, including the animals from Experiments 1 and 2, showed a quarterly rotation of pyrantel pamoate (June), IVM (September), larvicidal FBZ (December), and MOX (March) effectively reduced or broke resistance to FBZ, based on FECR tests. The mean FECR for the treatments were 95.86, 100, 97.84, and 100, respectively. These studies indicate that neither frequent use nor larger doses of FBZ will alleviate a FBZ resistance problem in the horse. However, Experiment 3 demonstrated that a rotational regimen can effectively break or reduce FBZ resistance and that FBZ can be successfully implemented in a rotational scheme subsequent to prior resistance.