BACKGROUND: The persistence of donor cells derived from the graft (chimerism) has been documented in various tissues after organ transplantation. It was suggested that stable chimerism might reflect a state of donor-specific tolerance. Chimerism of macrophages and lymphocytes were studied over time after lung transplantation as well as its impact on graft tolerance. MATERIAL AND METHODS: Macrophages and lymphocytes were purified from bronchoalveolar lavage sequentially obtained from 24 patients between 1 and 41 months posttransplantation (20, 22, 24, and 17 patients at, respectively, 1, 3, 6, and 12 months). DNA was extracted from these cells and their recipient-donor origin was evaluated by PCR amplification of highly polymorphic DNA regions (minisatellites). RESULTS: We show that the remaining donor cells over the first month vary from 10 up to 50% and 5 up to 55% for lymphocytes and macrophages respectively (+/-2 SD). All patients presented some chimerism up to the 6th postoperative month. Good correlation was observed between the residual amount of donor lymphocytes and macrophages during the first 3 months (P<0.001). Patients with at least 30% donor lymphocytes at 1 month after transplantation had less rejections (> or =stage II) in the follow up (P=0.0007). The same observation is true for donor macrophages although to lower extend (P=0.02). The chimerism lost its predictive value beyond 3 months. CONCLUSIONS: These data demonstrate that a level of chimerism above 30% of either donor lymphocytes or macrophages at 1 month is related to a better state of graft tolerance. However, chimerism decreases markedly beyond 3 months and has then no predictive value.