The effect of antiproximal tubule basement membrane (TBM) and brush border (BB) antibodies on p-aminohippurate (PAH) transport was evaluated in a rat model of immunologically mediated interstitial nephritis. Immunized rats developed anti-TBM antibody titers ranging from 1 to 3,072 with continuous linear IgG and interrupted C3 deposits in the TBM. Circulating anti-BB antibodies were detected in half of the immunized rats in titers ranging from 1 to 128. Heavy IgG deposition was present in the BB when circulating anti-BB antibody titers exceeded eight and proteinuria was present. When anti-TBM antibody titers were 1,024 or greater the slice-to-medium PAH concentration ratio (S/M) was significantly reduced (p < 0.001). Combined immunofluorescent microscopy and section freeze-dry autoradiography revealed normal cellular distribution of PAH-3H in all proximal tubules except in rare microscopic foci of interstitial nephritis in which concentrative transport was absent. However, luminal secretion of PAH-3H was strikingly reduced in tubules with heavy IgG BB deposits. 3-hour PAH excretion in vivo fell significantly in rats with circulating and tissue anti-BB antibodies. Antibody inhibition of PAH transport appeared to be independent of morphologic damage. Summary: Anti-TBM antibodies were associated with decreased slice uptake of PAH-3H while anti-BB antibodies were associated with decreased luminal PAH secretion in vitro and in vivo.