Interstitial fibrosis and tubular basement membrane (TBM) thickening are evident within 16 days of unilateral ureteral obstruction (UUO) in the rabbit, and resemble the changes previously reported in hydronephrotic human kidneys. The cortical interstitial volume fraction in this rabbit model at 16 days is 43.3 +/- 6.1% (+/- 1 SD) in UUO kidneys, 4.9 +/- 3.1% in contralateral kidneys (CLK), and 2.8 +/- 0.8% in kidneys from sham-operated animals (ANOVA, P < 0.0001). Immunohistochemically, UUO is associated with increased interstitial collagens I and III, fibronectin, heparan sulfate proteoglycan and tubulointerstitial nephritis antigen. Aberrant collagen expression is also evident as interstitial collagen IV becomes prominent. Focal, peritubular accumulation of collagens I and II also appear to encircle the TBM. These changes are accompanied by an early, transient increase in renal cortical mRNA encoding the alpha 1 monomers of collagens I, III and IV, implicating increased matrix synthesis in the pathogenesis of obstructive nephropathy. In situ hybridization localized increased expression of alpha 1 (I) and alpha 1 (IV) mRNA to cells in the interstitial space, with clusters of alpha 1(I) positive cells associated with dilated tubules, muscular arteries and the periglomerular interstitium.