Beef-type calves (n = 107) with naturally occurring helminth infections were used in a series of 3 controlled experiments to study the anthelmintic activity of a new pour-on formulation of levamisole. In the 1st experiment, the efficacy of a single treatment of levamisole pour-on at a rate of 10 mg/kg of body weight was determined, using a placebo pour-on in a similar volume as a control. In the 2nd experiment, calves were treated with levamisole pour-on at doses 0 (nontreated control), 7.5, 10, or 12.5 mg/kg of body weight. In the 3rd experiment, the anthelmintic efficacy of the optimal dose of levamisole pour-on (10 mg/kg of body weight) was compared with that of injectable levamisole at the recommended rate (6 mg/kg of body weight). In all 3 studies, levamisole pour-on, at a dosage of 10 mg/kg of body weight, was efficacious (90% to 100%) against the adult forms of Trichostrongylus axei, Haemonchus placei, Ostertagia ostertagi, Cooperia spp, Oesophagostomum radiatum, Nematodirus spp, and Bunostomum phlebotomum. Efficacy was moderate to good against Capillaria bovis, and poor or inconsistent against Strongyloides papillosus and Trichuris ovis. Clinical tests of anthelmintic efficacy and local tolerance of levamisole pour-on were conducted in 371 beef and dairy cattle in Mexico. Fecal egg counts were consistently reduced 2 weeks after a single application of levamisole pour-on at a dosage of 10 mg/kg of body weight. Local reactions were limited to various degrees of dry hair coat for up to 2 weeks at the application site. Hair loss or skin abnormalities were not observed in any of the treated cattle.