Background: Intravascular ultrasound (IVUS) measures prognostically important pulsatile flow indexes in patients with pulmonary hypertension (PH). IVUS catheters traditionally require a guiding catheter for placement which can impact hemodynamics in small infants because the guiding catheter renders the atrioventricular valve incompetent. Methods: Domestic swine (1.4-2.2 kg) were raised in isobaric normoxia (n = 4) or hypoxia (n = 3, FiO(2) 10-12%) for 72 hr for induction of PH. Cardiac catheterization and intravascular imaging was performed using a 3.5-Fr 20-MHz Eagle Eye Gold catheter (Volcano Corp., CA, USA) over a 0.014 '' guide wire. Intima-media thickness (IMT) was measured and relative area change and vascular pulsatility were calculated. Results: The IVUS probe was easily manipulated over a 0.014 '' wire without hemodynamic compromise in all animals. The IMT was thicker in the hypoxic group than the normoxic group (0.19 +/- 0.03 mm vs. 0.31 +/- 0.04 mm, p = .067). Hypoxic animals had systolic PH (39.66 +/- 2.51 vs. 21.75 +/- 2.87 mmHg, p = .02). Systemic arterial pressures between the groups were the same (hypoxic 68 +/- 10.44 vs. normoxic 79.75 +/- 14.84 mmHg, p = .26). Vascular pulsatility was similar (hypoxic 24 +/- 2.64 vs. 20.25 +/- 0.57%, p = .18). However, the arterial wall distensibility was significantly different (0.98 +/- 0.2 vs. 2.01 +/- 1.38 %/mmHg, p = .04). Conclusions: Monorail IVUS imaging without a guide catheter overcomes a major limitation for use in infants and small animal experimental models by avoiding hemodynamic compromise. This would be a valuable tool for assessment of PH in the research and clinical setting.