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P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are co-localized at the blood–brain barrier, where they display functional redundancy to restrict the brain distribution of dual P-gp/BCRP substrate drugs. We used positron emission tomography (PET) with the metabolically stable P-gp/BCRP substrates [¹¹C]tariquidar, [¹¹C]erlotinib, and [¹¹C]elacridar to assess whether a similar functional redundancy as at the BBB exists in the liver, where both transporters mediate the biliary excretion of drugs. Wild-type, <i>Abcb1a/b^(−/−)</i>, <i>Abcg2^(−/−)</i>, and <i>Abcb1a/b^(−/−)Abcg2^(−/−)</i> mice underwent dynamic whole-body PET scans after i.v. injection of either [¹¹C]tariquidar, [¹¹C]erlotinib, or [¹¹C]elacridar. Brain uptake of all three radiotracers was markedly higher in <i>Abcb1a/b^(−/−)Abcg2^(−/−)</i> mice than in wild-type mice, while only moderately changed in <i>Abcb1a/b^(−/−)</i> and <i>Abcg2^(−/−)</i> mice. The transfer of radioactivity from liver to excreted bile was significantly lower in <i>Abcb1a/b^(−/−)Abcg2^(−/−)</i> mice and almost unchanged in <i>Abcb1a/b^(−/−)</i> and <i>Abcg2^(−/−)</i> mice (with the exception of [¹¹C]erlotinib, for which biliary excretion was also significantly reduced in <i>Abcg2^(−/−)</i> mice). Our data provide evidence for redundancy between P-gp and BCRP in controlling both the brain distribution and biliary excretion of dual P-gp/BCRP substrates and highlight the utility of PET as an upcoming tool to assess the effect of transporters on drug disposition at a whole-body level.