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Background: We aimed to validate a low-dose two-volume pulmonary computed tomography (CT) perfusion technique., Methods: Five Yorkshire swine (weight 53.6 ± 2.6 kg) underwent 21 independent CT perfusion acquisitions. Intravenous contrast material (370 mg/mL iodine, 0.5 mL/kg) and saline chaser (0.5 mL/kg) were injected at 5 mL/s for each acquisition. Two-volume and multivolume dynamic CT perfusion data were acquired using a 320-slice CT, with multivolume measurements serving as the reference standard. The two-volume CT perfusion involved a low-dose (50 mA) volume scan before contrast injection and a diagnostic (300 mA) volume scan after bolus-tracking in the main pulmonary artery at the peak contrast enhancement. Multivolume CT perfusion included 15-20 volume scans for blood flow measurement. Paired sample t-test, linear regression, and Bland-Altman analysis compared both global and regional two-volume perfusion measurements to the reference standard. The reproducibility of the two-volume CT perfusion was assessed from two independent measurements under the same perfusion condition., Results: Two-volume global perfusion measurements (P 2V ) were related to reference multivolume (P MV ) measurements by P 2V  = 0.96 × P MV  + 0.45 (r = 0.92), with a root-mean-square error of 1.29 mL/min/g and a root-mean-square deviation of 1.29 mL/min/g. The CT dose index for the two-volume and multivolume CT perfusion measurements were 9.3 mGy and 184.8 mGy, respectively., Conclusion: We successfully validated a prospective, two-volume CT perfusion technique in a swine model. The findings affirm the feasibility of accurate and reproducible pulmonary blood flow measurement., Relevance Statement: This two-volume CT pulmonary perfusion technique, validated in a swine model, demonstrates the feasibility of blood flow measurement with a substantial reduction in radiation exposure. It could allow low-dose regional blood flow measurement in the assessment of pulmonary artery disease in humans., Key Points: Lung perfusion can be measured in mL/min/g using a prospective, two-volume CT technique. Flow measurement is achievable in a swine model with a radiation dose as low as 9.3 mGy. CT angiography and perfusion can be acquired following a single contrast injection., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Institutional Animal Care and Use Committee (IACUC, protocol number: AUP-18-191). Consent for publication: Not applicable. Competing interests: SM has received research grants from Canon Medical Systems. The remaining authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article., (© 2025. The Author(s).)