Inclusion Criteria:

   - Diagnosis of CF by newborn screening or at least one clinical feature of CF, AND
   either: (a) A documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine
   iontophoresis or (b) A genotype with two identifiable CF-causing mutations

   - Informed consent by parent or legal guardian

   - Age 4 months to < 60 months at Enrollment visit. If participating in Infant Pulmonary
   Function testing (selected sites), age 4 months to < 16 months at Enrollment visit.

   - Ability to comply with medication use, study visits, and study procedures as judged by
   the site investigator

Exclusion Criteria:

   - Acute intercurrent respiratory infection, defined as an increase in cough, wheezing,
   or respiratory rate with onset in 1 week preceding Enrollment visit

   - Acute wheezing at Enrollment visit (prior to HS test dose), or at Infant PFT visit
   (prior to infant pulmonary function testing), as applicable

   - Oxygen saturation < 95% (< 90% in centers located above 4000 feet elevation) at
   Enrollment visit (prior to HS test dose) or at Infant PFT visit (prior to infant
   pulmonary function testing), as applicable

   - Other major organ dysfunction, excluding pancreatic dysfunction

   - Physical findings that would compromise the safety of the subject or the quality of
   the study data as determined by the site investigator

   - Investigational drug use within 30 days prior to Enrollment visit, or within 30 days
   prior to Infant PFT visit as applicable

   - Treatment with inhaled hypertonic saline at any concentration within 30 days of
   Enrollment visit, or within 30 days prior to Infant PFT visit as applicable

   - Chronic lung disease not related to CF

   - Intolerance of test dose of HS at Enrollment visit

   - A sibling that has been randomized and is still enrolled in ISIS002

Additional Exclusion Criteria for Participation in Infant Pulmonary Function Testing:

   - History of adverse reaction to sedation

   - Clinically significant upper airway obstruction as determined by the Site Investigator
   (e.g. severe laryngomalacia, markedly enlarged tonsils, significant snoring, diagnosed
   obstructive sleep apnea)

   - Severe gastroesophageal reflux, defined as persistent frequent emesis despite
   anti-reflux therapy

   - Acute intercurrent respiratory infection, defined as an increase in cough, wheezing,
   or respiratory rate with onset in 2 weeks preceding visit