This paper describes an exceptional spectrum of multiple anthelmintic resistance in two strains of Haemonchus contortus in South Africa, one from Howick in KwaZulu-Natal, and the other from Badplaas, in Mpumalanga. Apparently for the first time, a helminth strain is described with resistance to compounds from all five of the modern anthelmintic groups used for nematode control in sheep; also, two strains of H. contortus show resistance to the two substituted phenols, dinitrophenol and nitroxynil. Only closantel at 5 mg kg-1 of nine compounds tested appears to have undiminished efficacy against the Howick strain, but even in the case of closantel, the residual activity and minimal effective level need to be tested before it can be concluded that its efficiency is unaffected. The exceptional resistance of the Howick strain is demonstrated by the fact that sequential daily drenching of sheep infected with the strain, with levamisole at 18 mg kg-1, oxfendazole at 20 mg kg-1, levamisole at 20 mg kg-1 and a mixture of fenbendazole at 10 mg kg-1 plus trichlorfon at 132 mg kg-1 on the fourth day, failed to clear sheep of the infection. There are strong indications that side-resistance occurs between dinitrophenol and nitroxynil, on the one hand, and the salicylanilides, on the other, and it is suggested that, before long, strains of H. contortus will be found with high levels of resistance to all the currently available anthelmintics.