While dose dependencies in pharmacokinetics andclearance are often observed in clinically used small molecules,very few studies have been dedicated to the understandings ofpotential dose-dependent in vivo transport of nanomedicines.Here we report that the pharmacokinetics and clearance ofrenal clearable gold nanoparticles (GS-AuNPs) are stronglydose-dependent once injection doses are above 15 mgkg @1 :high dose expedited the renal excretion and shortened theblood retention. As a result, the no-observed-adverse-effect-level (NOAEL) of GS-AuNPs was >1000 mgkg @1 in CD-1 mice. The efficient renal clearance and high compatibility canbe translated to the non-human primates: no adverse effectswere observed within 90 days after intravenous injection of250 mgkg @1 GS-AuNPs. These fundamental understandings ofdose effect on the in vivo transport of ultrasmall AuNPs openup a pathway to maximize their biomedical potentials andminimize their toxicity in the future clinical translation.