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Resistance to modern anthelmintics by ruminant nematode parasites is an increasing problem throughout the world. To date the problem has largely been reported in parasites of small ruminants, but there are increasing reports of such resistance in nematodes recovered from cattle. Until now there have been no published reports of drug resistant parasites from cattle in North America. In 2002 a producer in the upper Midwest who backgrounds young cattle acquired from the southeastern US experienced lower than expected weight gain as well as apparent parasitic gastroenteritis in his cattle during the fall. Fecal sample results supported the suspicion that decreased productivity and diarrhea were the result of GI nematode parasitism. The operation used intensive grazing management and practiced strategically timed deworming for >17 years. In 2003, all animals were dewormed the first week of May with Ivomec Plus®, then with Dectomax® Injectable on 4 June and 17 July. On 31 July, 10 randomly taken fecal samples showed EPG values from 0 to 55. To assess whether the apparent decreased drug efficacy was the result of drug resistance in the nematode population, on 18 August approximately 150 heads, previously strategic timed dewormed, of 9–11 month old cattle from one pasture were selected for study. The calves were randomly assigned to 1 of 6 treatment groups: untreated (U), ivermectin injectable (I), moxidectin pour-on (M), doramectin injectable (D), eprinomectin pour-on (E), albendazole oral (A). Cattle were weighed prior to treatment and the drug was dosed according to label directions. Seven days later, 3 calves from each group were slaughtered for worm recovery. Fecal samples taken from the remaining animals at 14 days after treatment showed that the reduction of mean fecal EPG value for each group was: U-46%, I-52%, M-72%, D-61%, E-8%, and A-68%. Worm recovery from the slaughter calves showed that all groups harbored significant numbers of Haemonchus placei and H. contortus. In addition, all avermectin-treated groups contained significant numbers of Cooperia punctata, and smaller numbers of C. oncophora and C. spatulata. These results imply that the pastures studied contain substantial numbers of H. contortus resistant to both avermectins and benzimidazoles, and H. placei and Cooperia sp. resistant to all the commonly used avermectin anthelmintics. This is the first report of anthelmintic resistance in American cattle parasites.