The expression of drug resistance antigens in mononuclear inflammatory cells was studied in transbronchial lung biopsy specimens of lung allograft recipients who experienced steroid-sensitive and steroid-resistant bouts of acute rejection and bronchiolitis obliterans. Immunostains for C494 and C219 epitopes of p-glycoprotein and human metallothionein revealed that (1) mononuclear cells expressing these antigens are present in the lung allograft during rejection, (2) that steroid-resistant acute rejection is associated with increased percentages of C494 and metallothionein-positive cells as compared to steroid-sensitive cases, (3) that bronchiolitis obliterans was associated with a higher percentage of cells with drug-resistant antigen expression, and (4) that steroid-resistant bronchiolitis obliterans is associated with the highest percentage of C494 and metallothionein-positive cells in the five clinical situations studied. P-glycoprotein and metallothionein expression may be a marker of aggressive or persistent cases of acute rejection and bronchiolitis obliterans.