The effect of experimentally induced acute renal failure (ARF) on neuronal cell activation was investigated by immunohistochemistry for Fos and Fra-2 in the rat brain. ARF in rats was induced by bilateral nephrectomy (BNX), bilateral ureter ligature (BUL) and uranyl acetate injection with proper controls (sham-operation or saline injections, respectively). To follow the effect of the development of ARF, rats were killed 30 and 60 min, and 3, 12, 24 and 72 h after surgery, or 3 h to 12 days after uranyl acetate injections. In the BUL and BNX rats, urea and creatinine rose markedly in the plasma within 72 h, while in the uranyl acetate-injected rats the highest levels were observed on the 7th day, followed by a marked decline. At each time-point of the three different, experimentally induced ARF, the presence of Fos- and/or Fra-2-immunoreactive neurons was determined in 120 different brain areas and nuclei. In general, the 73 of 120 brain areas that showed time and intensity dependent activation in response to ARF can be classified into four groups: 1) biogenic amine (noradrenaline, adrenaline, histamine and 5-HT) expressing cell groups in the lower brainstem, 2) "stress-sensitive" forebrain areas, with regard to certain hypothalamic, limbic and cortical areas, 3) neuronal cell groups that participate in the central regulation of body and brain water and electrolyte homeostasis, including the circumventricular organs, and 4) central autonomic cell groups, especially visceral sensory cell groups in the brain, which are in primary, secondary or tertiary connections with renal afferents. Data presented here indicate that a wide variety of neurons in several regulatory mechanisms is affected by ARF-induced peripheral and central alterations.