Using bronchoalveolar lavage (BAL) we evaluated the concentration-time profile of tobramycin in the alveolar lining fluid (ALF) of rats after direct endotracheal instillation (1.5 mg/kg) and aerosolization (10 mg/ml for 15 min). Very high and long-persisting concentrations of tobramycin were reached in ALF after both modes of administration. After aerosolization a peak concentration in ALF of 339 +/- 41 micrograms/ml was reached with a slow but progressive decline to 45 +/- 8 micrograms/ml at 6 h. After direct endotracheal instillation significantly higher (p less than 0.01) concentrations in ALF (peak concentration, 2,100 +/- 16 micrograms/ml) were reached and formed a stable plateau until 4 h after administration, progressively declining thereafter (400 +/- 30 micrograms/ml at 6 h). Systemic vascular absorption from the alveoli was minimal, but it was higher after direct endotracheal instillation (peak serum concentration, 1.55 +/- 0.21 micrograms/ml). We conclude that in view of the favorable pharmacokinetic profile and the minimal systemic absorption, endobronchial administration of aminoglycosides may be a valuable alternative to systemic administration, which eventually can reduce systemic toxicity and the need for therapeutic drug monitoring.