The adverse effects of elevated polybrominated diphenyl ether (PBDE) levels, reported in the blood of domestic dogs and cats, are considered to be of great concern. However, the tissue distribution of PBDEs and their derivatives in these animals is poorly understood. This study determined the concentrations and profiles of PBDEs, hydroxylated PBDEs (OH-PBDEs), methoxylated PBDEs (MeO-PBDEs), and 2,4,6-tribromophenol (2,4,6-tri-BPh) in the blood, livers, bile, and brains of dogs and cats in Japan. Higher tissue concentrations of PBDEs were found in cats, with the dominant congener being BDE209. BDE207 was also predominant in cat tissues, indicating that BDE207 was formed via BDE209 debromination. BDE47 was the dominant congener in dog bile, implying a species-specific excretory capacity of the liver. OH-PBDE and MeO-PBDE concentrations were several orders of magnitude higher in cat tissues, with the dominant congener being 6OH-BDE47, possibly owing to their intake of naturally occurring MeO-PBDEs in food, MeO-PBDE demethylation in the liver, and lack of UDP-glucuronosyltransferase, UGT1A6. Relatively high concentrations of BDE209, BDE207, 6OH-BDE47, 2'MeO-BDE68, and 2,4,6-tri-BPh were found in cat brains, suggesting a passage through the blood brain barrier. Thus, cats in Japan might be at a high risk from PBDEs and their derivatives, particularly BDE209 and 6OH-BDE47.