This study compares plasma disposition kinetics of ivermectin and moxidectin after oral administration to beagle dogs experimentally infected with the filarial parasite, Brugia pahangi. Sixteen dogs were selected and randomly allocated into two groups of eight dogs each. Animals in each group received either ivermectin or moxidectin by oral route at a dose of 250 µg/kg. Blood samples were collected from 0.5 h up to 56 days post-treatment and the plasma was analysed by high performance liquid chromatography (HPLC). The obtained data were analysed by compartmental and non-compartmental pharmacokinetic techniques. Peak plasma concentrations (Cmax) of 234.0 ± 64.3 ng/ml (mean ± SD) were obtained for moxidectin and 132.6 ± 43.0 ng/ml for ivermectin. The terminal elimination half-life was significantly (p<0.01) longer in the moxidectin treated group (621.3 ± 149.3 h) than for ivermectin treated group (80.3 ± 29.8 h). A significantly (p< 0.01) larger Vss/F was obtained for moxidectin (19.21 ± 3.61 l/kg) compared with ivermectin (5.35 ± 1.29 l/kg). The mean estimates of CL/F of moxidectin and ivermectin were 0.0220 ± 0.00381 and 0.0498 ± 0.0179 l/h/kg, respectively. The comparative plasma disposition kinetics of ivermectin and moxidectin in dogs is reported for the first time. Copyright © 2007 John Wiley & Sons, Ltd.