To date, there has been neither a good method to clarify the three-dimensional distribution of pulmonary ventilation/perfusion (V. A/Q.) ratios, nor a convenient way to assess V.A/Q. inequality. The purpose of this study was to develop a functional image of pulmonary V.A/Q. ratios based on data acquired with simultaneous dual-radionuclide single-photon emission tomography (SPET) and to assess V.A/Q. unevenness through the V.A/Q. histogram in patients with various pulmonary diseases. Dual-radionuclide SPET was performed with technetium-99m macroaggregated albumin (MAA) and krypton-81m, with the patient in the supine position. After correction for linear cross-talk, the total acquisition counts of both radionuclides were equalized. The V.A/Q. ratio, which was calculated in each pixel by dividing the 81mKr count by the 99mTc-MAA count, was expressed as a V.A/Q. image. A histogram of the pixel number plotted against the V.A/Q. ratios was then produced and its centre of weight (CW) and standard deviation (SD) determined. Ten healthy volunteers and 46 patients [seven with pulmonary vascular disease (PVD), nine with pulmonary emphysema (PE), 18 with bronchogenic carcinoma and 12 with miscellaneous diseases] participated in this study. In normal volunteers, V.A/Q. ratios were generally even, but were slightly lower in dorsal regions. Patients with PVD had lobar and/or segmental areas with a high V.A/Q. ratio. Low V.A/Q. areas extended widely in patients with PE. Bronchogenic carcinoma exceeding 3 cm in diameter was detected as a very low V. A/Q. area. The SD of V.A/Q. ratios had a significant positive correlation both with A-aDO2 (r=0.64, P<0.001) and with cigarette smoking history (r=0.72, P<0.001). It is concluded that the V.A/Q. ratio image produced with simultaneous dual-radionuclide SPET using 99mTc-MAA and 81mKr is a unique and simple method for demonstrating the three-dimensional distribution of V.A/Q. ratios. The unevenness of V.A/Q. distribution can be assessed through the SD of the V.A/Q. histogram.