Effects of reduced renal perfusion pressure and acute volume expansion on proximal tubule and whole kidney angiotensin II content in the rat. In previous studies high luminal concentrations of angiotensin II (Ang II) were found in rat proximal tubules. The physiological role of intraluminal Ang II remains to be established. In the present study, we investigated whether the luminal angiotensin II concentration in the proximal tubules ([Ang II]_prox) can be modulated. Micropuncture studies were performed in control rats (C, N = 8) and rats subjected to acute volume expansion (VE, N = 8) or reduced renal perfusion pressure (RRP, N = 7). Changes in [Ang II]_prox were compared to changes in whole kidney Ang II content ([Ang II]_kidney) and the plasma concentration ([Ang II]_plasma). In C rats, [Ang II]_prox was 460 ± 48 pmol/liter (10 to 20 times lower than hitherto reported), while [Ang II]_kidney and [Ang II]_plasma were 369 ± 81 pmol/kg and 90 ± 29 pmol/liter, respectively. In agreement with previous data, VE failed to suppress [Ang II]_prox (674 ± 132 pmol/liter), while at the same time [Ang II]_kidney (42 ± 10 pmol/kg) and [Ang II]_plasma (12 ± 3 pmol/liter) were markedly suppressed. This points to dissociated regulation of [Ang II] in the renal luminal compartment on the one hand and the extraluminal renal and systemic plasma compartments on the other hand. During RRP, [Ang II]_prox increased significantly to 1675 ± 465 pmol/liter. No dissociation between the three compartments was observed in this situation, as [Ang II]_kidney (969 ± 85 pmol/kg) and [Ang II]_plasma (245 ± 72 pmol/liter) increased in parallel. In summary, we confirm that Ang II is present in proximal tubules of rat kidneys at concentrations which exceed those in plasma. Its concentration could be modulated (∼3.5 increase) by reduction of renal perfusion pressure but not by acute volume expansion. In the latter condition, we observed a clear dissociation from Ang II generation in the extraluminal renal compartment, as whole kidney Ang II content was markedly suppressed.