Steers were treated with doramectin or eprinomectin by daily oral capsule for 28 consecutive days. The level of doramectin in the serum of steers treated at 200 µg/kg/d reached a maximum of 104.0 ± 22.1 ppb at day 21 and declined from 93.3 ± 20.5 ppb on the final day of treatment to below detectable by day 56. Steers treated at 50 µg/kg/d reached a maximum level of doramectin in the serum of 24.7 ± 1.2 ppb on day 21 and declined from 24.7 ± 0.6 ppb on the final day of treatment to less than detectable on day 42. Both doramectin dosages provided 100% control of estimated larvae (EL) of Amblyomma americanum (L.) (Acari: Ixodidae) throughout the 28-d treatment period. Daily oral treatment with eprinomectin at a dosage of 200 µg/kg for 28 consecutive days produced a maximum concentration in the serum of 41.6 ± 11.0 ppb at day 14. On the final day of eprinomectin treatment, the serum concentration was 38.3 ± 5.9 ppb. Seven days later at day 35, eprinomectin was not detectable in the serum. For steers treated at 50 µg/kg/d for 28 consecutive days, the serum level of eprinomectin reached a maximum of 10.0 ± 3.0 ppb on day 28 and was undetectable on day 35. Both eprinomectin dosages provided complete control of EL of A. americanum during the 28-d treatment period. Because eprinomectin is efficacious against A. americanum at lower serum levels in cattle and is eliminated from the serum at a more rapid rate than either doramectin or ivermectin, it provides advantages for use in applications such as the medicated bait for control of ticks on white-tailed deer and could have potential for use in the Cattle Fever Tick Eradication Program.