Advocate (moxidectin 2.5% + imidacloprid 10%) is a multiparasiticidal agent authorized for treating canine demodicosis in many countries. This blind, randomized clinical trial assessed the efficacy of Advocate at varying treatment intervals and compared it with that of oral ivermectin. Fifty dogs with generalized demodicosis were randomly assigned to one of four treatment groups: oral ivermectin (500 microg/kg once daily), Advocate applied at the authorized dose monthly (ADV1), every 2 weeks (ADV2) or weekly (ADV4). Each dog was evaluated every 4 weeks for 4 months or until negative scrapings at all sites resulted on two successive evaluations (parasitological cure). Miticidal efficacy was determined through deep skin scrapings taken from the same three sites on each occasion. Total numbers of live and dead adult mites, juveniles and eggs were determined. Thirty-five dogs completed the 4-month trial. Parasiticidal efficacy was assessed using several parameters including reduction in live adult mite counts. ancova analysis for this parameter confirmed that there were differences in efficacy among the treatment groups (P < 0.002). Tukey-Kramer all pairwise multiple comparison tests revealed that ADV4 was more effective than ADV1 (P = 0.016). Ivermectin was more effective than ADV1 (P = 0.003). Both ivermectin and ADV4 showed clinically substantial reductions in adult mite counts (89% for ADV4 and 98% for ivermectin). In conclusion, the efficacy of Advocate increased with the rate of application and weekly application may represent a new approach to the treatment of caninegeneralized demodicosis.