A case of nonlinear desipramine pharmacokinetics is described. During routine clinical monitoring serum desipramine concentrations appeared to change disproportionately with dose. Following a series of controlled dosage decreases, from 400 to 50 mg/day, the patient's steady state serum concentrations fit a nonlinear pharmacokinetic model. This curvilinear serum concentration-dose relationship suggests saturation of hepatic metabolism and signals the need for caution when predicting or titrating doses against serum drug concentrations. The implications of this new finding are discussed.