This report describes the treatment of resistant gram-negative pneumonitis in a compromised host by the combined use of intravenous and endotracheal tobramycin. The endotracheal administration appeared to have an effect on the serum concentration and elimination rate, necessitating a reduction in the amount of drug given intravenously. The only apparent clinical complication of endotracheal drug administration was transient coughing. The addition of endotracheal aminoglycosides to intravenous antibiotics may be useful in pediatric patients with unresponsive (or other difficult-to-treat) pneumonitis caused by resistant microorganisms. The potential contribution of endotracheal aminoglycosides to the serum level and/or disposition profile must be recognized, and therapeutic drug monitoring guided accordingly when this route of administration is used.