Two controlled studies involving 24 cattle were conducted in New Zealand to determine the efficacy of a topical, non-flammable formulation of eprinomectin against induced and naturally acquired nematode infections. In Trial 1, nematode infections were induced on Day -5 with third-stage larvae of Cooperia spp., Haemonchus contortus, Ostertagia ostertagi and Trichostrongylus colubriformis so that the nematodes would be at the fourth larval stage when the cattle were treated. In Trial 2, cattle had naturally acquired nematode infections as determined by faecal nematode egg counts and larval cultures. The cattle were allocated on Day 0 (Trial 1) or Day -6 (Trial 2) on a stratified random basis according to bodyweight to one of two treatments: untreated control or eprinomectin (0.5% w/v) applied topically at 1 ml/l0 kg bodyweight. Necropsies were undertaken on Days 14 and 15 and total nematode counts were done. In Trial 1, cattle treated with eprinomectin had significantly (p < 0.05) fewer Cooperia spp. and O. ostertagi than the controls. Larvae of H. contortus and T. colubriformis did not establish. In Trial 2, cattle treated with eprinomectin had significantly (p < 0.05) fewer of the following parasites than the controls: Haemonchus spp. (adult), Cooperia surnabada (adult), C. oncophora (adult), Cooperia spp. (L4), Ostertagia lyrata (adult), O. ostertagi (adult), Oesophagostomum spp. (adult), T. axei (adult and L4) and Trichuris spp. (adult). Reductions of 100% were observed for Capillaria spp. (adult), D. viviparus (adult and L4), and Nematodirus helvetianus (adult), but these were not statistically significant (p > 0.05) because four or fewer control animals were infected with these parasites. In Trial 2, efficacies of greater than 99% were observed against all species for which moderate to high burdens occurred in the untreated controls. These findings indicate that eprinomectin in a topical formulation is a highly effective nematocide in cattle.