A computerized model of creatinine kinetics was developed to predict the relationship between creatinine clearance [G(t)] and plasma creatinine concentration [C(t)] in patients with postischemic acute renal failure (ARF). A comparison of predicted to measured values in 35 episodes of ARF in 27 patients revealed three patterns of declining G(t) following an ischemic insult. Pattern A, characterized by an abrupt step decrement in G(t) following an isolated renal ischemic episode lasting minutes or hours, was observed in nine patients. It was followed invariably by an immediate ramp increment in G(t), despite which C(t) continued to increase for several days. Urinary indices during the period of increasing azotemia were consistent with the resolving stage of ARF. Patterns B (N = 15) and C (N = 11) were associated with persistent renal ischemia of long (days to weeks) duration and were respectively characterized by prolonged ramp or exponential decrements in G(t). A concurrent increase in C(t) was associated with urinary indices typical of the maintenance or sustained stage of ARF. Recovery of G(t) was observed in only two-thirds of patterns B and C cases and took the form of a ramp or exponential increment. Because G(t) and total body water were changing rapidly in ARF, changes in measured plasma creatinine levels alone failed to identify these patterns of deteriorating or improving renal function. However, when the computerized model was used in conjunction with daily measured values of C(t) and body weight and occasional estimates of G(t), the course and prognosis of ARF in individual patients were illuminated.