The accuracy of two equations in normalizing total phenytoin concentrations in the presence of renal failure or hypoalbuminemia was evaluated in 11 renal failure and 23 hypoalbuminemic patients. Blood samples were obtained from hospitalized patients receiving phenytoin and were assayed for free and total phenytoin concentrations. Estimated normalized phenytoin concentrations based on free drug concentration were compared statistically with normalized concentrations calculated from the two equations via Student's t-test. The equation for normalizing phenytoin concentrations in hypoalbuminemic patients significantly underpredicted normalized phenytoin concentrations 15.7 +/- 8.5 versus 19.9 +/- 12.1 mg/L (p less than 0.001). In patients with renal failure, the mean phenytoin concentration from the respective equations and that based on free concentration were 14.1 +/- 6.2 and 14.0 +/- 7.9 mg/L, respectively. However, in 5 of 11 renal failure patients the equation resulted in over- or underprediction by at least 25 percent. Neither equation should be used clinically to normalize phenytoin concentrations in these patient populations.