Objectives: To assess the serum and lower respiratory tract tobramycin concentrations (CT) produced by a single dose of tobramycin for inhalation delivered by a nebulizer and a compressor in patients with cystic fibrosis (CF) 6 months to 6 years of age. Study design: We performed a dose escalation study of serum CT measured before and 0.5, 1, 2, and 4 hours after a single dose of inhaled tobramycin, either 180 mg (10 patients) or 300 mg (19 patients). In a separate group of 12 patients, epithelial lining fluid (ELF) CT was measured by bronchoalveolar lavage 30 to 45 minutes after a 300-mg dose. Results: A 180-mg dose of inhaled tobramycin produced a mean peak serum CT of 0.5 μg/mL (SD 0.4; range, <0.2 to 1.4 μg/mL). A 300-mg dose produced a mean peak serum CT of 0.6 μg/mL (SD 0.5; range, <0.2 to 1.2 μg/mL). These peak values are well below the accepted maximum trough concentration with parenteral dosing (2 μg/mL). The target ELF CT was 20 μg/mL, 10-fold greater than the minimal inhibitory concentration for most Pseudomonas aeruginosa isolates from very young patients with CF (2 μg/mL). Mean ELF CT was 90 μg/mL (SD 54; range, 16 to 204 μg/mL) and exceeded the target concentration in 11 patients. Conclusion: In patients with CF ages 6 months to 6 years, a single 300-mg dose of inhaled tobramycin appears to produce safe peak serum concentrations and drug concentrations in the bactericidal range in the lower respiratory tract. (J Pediatr 2001;139:572-7)