BACKGROUND: Fluorine-enhanced MRI is a relatively inexpensive and straightforward technique that facilitates regional assessments of pulmonary ventilation. In this report, we assess its suitability through the use of perfluoropropane (PFP) in a cohort of human subjects with normal lungs and subjects with lung disease. METHODS: Twenty-eight subjects between the ages of 18 and 71 years were recruited for imaging and were classified based on spirometry findings and medical history. Imaging was carried out on a Siemens TIM Trio 3T MRI scanner using two-dimensional, gradient echo, fast low-angle shot and three-dimensional gradient echo, volumetric, interpolated, breath-hold examination sequences for proton localizers and PFP functional scans, respectively. Respiratory waveforms and physiologic signals of interest were monitored throughout the imaging sessions. A region-growing algorithm was applied to the proton localizers to define the lung field of view for analysis of the PFP scans. RESULTS: All subjects tolerated the gas mixture well with no adverse side effects. Images of healthy lungs demonstrated a homogeneous distribution of the gas with sufficient signal-to-noise ratios, while lung images from asthmatic and emphysematous lungs demonstrated increased heterogeneity and ventilation defects. CONCLUSIONS: Fluorine-enhanced MRI using a normoxic PFP gas mixture is a well-tolerated, radiation-free technique for regionally assessing pulmonary ventilation. The inherent physical characteristics and applicability of the gaseous agent within a magnetic resonance setting facilitated a clear differentiation between normal and diseased lungs.