The objective of this study was to evaluate the potential role for single photon-emission computed tomography (SPECT) using technetium 99m-macroaggregated albumin for diagnosing rejection in lung transplant patients. SPECT results were compared with those obtained from transbronchial biopsy (TBB) in patients undergoing bronchoscopy during routine surveillance and in cases of clinical, radiographic, or physiologic suspicion of lung rejection. This prospective, nonrandomized study was conducted by the Marseille Lung Transplant Group, Marseille University Hospitals South. It included 26 lung transplant recipients (19 double-lung, four single-lung, and three heart-lung). For each patient, SPECT lung perfusion was performed before TBB as part of routine surveillance protocol and when clinically indicated. Routine surveillance included TBB at 1, 3, 6, 9, and 12 months and every 6 months thereafter. SPECT was always performed within the 24 h preceding TBB. Whenever the SPECT was abnormal, biopsies were obtained from an area corresponding to a region of hypoperfusion. Results of the study were based on 79 paired SPECT and TBB obtained from 26 patients. Concordance between SPECT and biopsy occurred in 71 instances (89.9%). Among 25 cases of normal SPECT, TBB was normal in 24 and revealed subclinical lung rejection in one. Among 54 cases of abnormal SPECT, TBB was also abnormal in 47 (87.0%), with lung rejection being the abnormality in 23 (46%). For pairs performed as part of the routine surveillance protocol (61 pairs), clinically silent lung rejection was diagnosed in 16 (26.2%). SPECT was abnormal in 15 of 16 instances and normal in only one; this patient had minimal rejection that resolved without treatment.(ABSTRACT TRUNCATED AT 250 WORDS)