Twenty-six consecutive patients admitted to the medical ICU with presumed sepsis or septic shock had their initial serum aminoglycoside level determined 1 h after completion of a 20-min infusion of tobramycin, 2 mg/kg. There was a poor correlation between the dose received and the measured aminoglycoside level; 59% of the patients had initial blood aminoglycoside concentrations below the recommended peak level of 5 μg/ml. An underestimation of the volume of distribution in critically ill patients best explains the low serum aminoglycoside levels produced by the currently recommended dosage schedule.