Prior acute renal failure (ARF) induced by either glycerol (G) or mercury provides protection against rechallenge with the same agent or the other. To ascertain whether the widely employed ischemic renal failure model also shares a similar pathogenesis, two protocols were designed. In the first protocol, unilaterally nephrectomized rats with or without a prior episode of G-induced ARF two weeks previously were subjected to an ischemic insult [60-min total left renal artery clamp (LRAC)]. At 24 or 48 h after LRAC there was no difference in renal function in the rats with or without prior ARF. In the second protocol the sequence of G and ischemia was reversed. In rats having undergone LRAC two weeks prior to G, glomerular filtration rate was virtually identical from the right (control) and left (prior ARF) kidney (right, 138 ± 30; left, 101 ± 22 μl/min/100 g body weight), and not different from rats receiving G alone. We conclude that protection against ARF conferred by prior insult is not a feature of all models.