A morbidly obese woman [190kg total bodyweight (TBW)] was admitted to hospital with a rapidly progressing wound infection. Over the next 2 weeks the patient developed congestive heart failure, acute renal failure, septic shock and multiple seizure episodes. Intravenous phenobarbital was added to phenytoin therapy to achieve seizure control. A total loading dose of phenobarbital 3700mg (19.5 mg/kg TBW) was administered in 3 divided doses. The initial dose of 1100mg resulted in a serum phenobarbital concentration of 6.3 mg/L 5h postinfusion, a second 1100mg dose increased the concentration to 13.1 mg/L 1h postinfusion and a final dose of 1500mg resulted in a 22.5 mg/L concentration at the end of the infusion. A phenobartital maintenance regimen of 120mg every 12h was then started. Peak serum concentrations of 19.8 and 17.8 mg/L were measured. All of the available serum phenobarbital concentrations and dosage amounts were fitted with least-squares nonlinear regression analysis to a 1-compartment model. An apparent volume of distribution (Vd) of 154.9L (0.82 L/kg TBW), total body clearance (CL) of 29 ml/min (1.74 L/h) and elimination half-life of 61h were determined.Our case report suggests that the dose of intravenous phenobarbital should be calculated using TBW. Additional studies are needed to precisely define the appropriate dosage weight, serum concentrations and clinical efficacy associated with intravenous phenobarbital in morbidly obese patients.