Endobronchial ultrasonography (EBUS) with a radial scanning probe provides cross-sectional images of peripheral pulmonary lesions. We devised a technique of EBUS for the diagnosis of peripheral pulmonary lesions. EBUS using a thick guide sheath (GS) [2.5 mm in diameter] covering a miniature probe, and 150 lesions were evaluated in a prospective open study. In the procedure of EBUS-GS, the probe covered by a GS is introduced into the lesion via the working channel of a bronchoscope. The probe is withdrawn, while the GS is left in situ. A brush or biopsy forceps is introduced through the GS into the lesion. EBUS visualized the image in 93% of the peripheral pulmonary lesions. One hundred sixteen (77%) of 150 EBUS-GS procedures were diagnostic. Cases in which the probe was located within the lesion, had a significantly higher diagnostic yield (105/121, 87%) than when the probe was located adjacent to it (8/19, 42%). Diagnostic yield from EBUS-GS in lesions < or = 10 mm (16/21, 76%), 10<, < or = 15 mm (19/25, 76%, p=0.99, chi2), 15<, < or = 20 mm (24/35, 69%, p=0.41, chi2), and 20<, < or = 30 mm (33/43, 77%, p=0.96, chi2) were similar, demonstrating the efficacy of EBUS-GS even in lesions < or = 20 mm in diameter.