BACKGROUND: Prolonged slow expiration (PSE) is a physiotherapy technique often applied in infants to reduce pulmonary obstruction and clear secretions, but there have been few studies of PSE's effects on the respiratory system. OBJECTIVE: To describe PSE's effects on respiratory mechanics in infants. METHODS: We conducted a cross-sectional study with 18 infants who had histories of recurrent wheezing. The infants were sedated for lung-function testing, which was followed by PSE. The PSE consisted of 3 sequences of prolonged manual thoraco-abdominal compressions during the expiratory phase. We measured peak expiratory flow (PEF), tidal volume (V T ), and the frequency of sighs during and immediately after PSE. We described the exhaled volume during PSE as a fraction of expiratory reserve volume (%ERV). We quantified ERV with the raised-volume rapid-thoracic-compression technique. RESULTS: The cohort's mean age was 32.2 weeks, and they had an average of 4.8 previous wheezing episodes. During PSE there was significant V T reduction (80 ؎ 17 mL vs 49 ؎ 11 mL, P < .001), no significant change in PEF (149 ؎ 32 mL/s vs 150 ؎ 32 mL/s, P ؍ .54), and more frequent sighs (40% vs 5%, P ؍ .03), compared to immediately after PSE. The exhaled volume increased in each PSE sequence (32 ؎ 18% of ERV, 41 ؎ 24% of ERV, and 53 ؎ 20% of ERV, P ؍ .03). CONCLUSIONS: It was possible to confirm and quantify that PSE deflates the lung to ERV. PSE caused no changes in PEF, induced sigh breaths, and decreased V T , which is probably the main mechanical feature for mucus clearance.