Human organic anion transporter 1 (hOAT1) belongs to a family of organic anion transporters that play critical roles in the body disposition of clinically important drugs, including anti-HIV therapeutics, anti-tumor drugs, antibiotics, antihypertensives, and anti-inflammatories. hOAT1 is abundantly expressed in the kidney. In the current study, we examined the regulation of hOAT1 by angiotensin II (Ang II) in kidney COS-7 cells. Ang II induced a concentration- and time-dependent inhibition of hOAT1 transport activity. Such inhibition mainly resulted from a decreased cell surface expression without a change in total cell expression of the transporter, kinetically revealed as a decreased V_max without significant change in K_m. Ang II-induced inhibition of hOAT1 activity could be prevented by treating hOAT1-expressing cells with staurosporine, a general PKC inhibitor. To obtain further information on which PKC isoform mediates Ang II regulation of hOAT1 activity, cellular distribution of various PKC isoforms were examined in cells treated with or without Ang II. We showed that Ang II treatment resulted in a significant translocation of PKC from cytosol to membrane, and such translocation was blocked by treating hOAT1-expressing cells with Gö6976, a PKC-specific inhibitor. We further showed that Ang II-induced inhibition of hOAT1 activity and retrieval of hOAT1 from cell surface could also be prevented by treating hOAT1-expressing cells with Gö6976. We concluded that Ang II inhibited hOAT1 activity through activation of PKC, which led to the redistribution of the transporter from cell surface to the intracellular compartments.