Background: There is a significant need to estimate creatinine clearance easily in acutely ill patients with unstable renal function, who have rapidly changing serum creatinine values and who need careful individualization of drug dosage, all without the problems associated with having to collect the traditional carefully timed urine specimen. Method: The daily change in the total amount of creatinine is the difference between its production and excretion. Production is estimated based on studies by others, using many carefully timed urine specimens. Daily creatinine production is related both to age and to the serum creatinine concentration. Urinary excretion of creatinine is equal to creatinine clearance times the average of a pair of timed serum creatinine concentrations, times the duration of the collection (usually 24 h). Results: Good correlation was found between conventional measured creatinine clearances and the estimated values. The estimates had a precision essentially equal to that of the traditional method. Conclusions: One can now estimate the creatinine clearance which makes serum creatinine change from an initial concentration at one stated time to another concentration at another stated time, for a patient of a stated age, gender, height and weight, without requiring a urine specimen. This method has been incorporated into software to perform the calculations easily and rapidly, and has been integrated into the USC*PACK PC programs for planning, monitoring and adjusting individualized dosage regimens of drugs.