AbstractThe acute nephrotoxic effects of paracetamol in the uninephrectomized homozygous Gunn rat are different from those of aspirin. Both compounds induce renal papillary necrosis but paracetamol produces accumulation of non‐cellular material in the interstitial space, less damage to interstitial cells, more damage to tubular epithelium, and more severe necrosis of proximal convoluted tubules. In both cortex and papilla only a small fraction of the cells at risk are affected. It is concluded that the findings are consistent with a synergistic nephrotoxic effect between the two compounds, but that the lesions are not sufficiently severe for the natural history of analgesic nephropathy to be wholly explicable by such synergis