Pulmonary infections are a significant cause of morbidity after liver transplantation; Gram-negative bacilli, cytomegalovirus, andPneumocystis carinii were the usual pulmonary pathogens in the earlier studies in liver transplant recipients receiving cyclosporine. We prospectively assessed the impact of pulmonary infections in 101 consecutive liver transplant recipients receiving the new immunosuppressive agent tacrolimus (FK506). Fifteen percent (15/101) of the patients had 19 episodes of pneumonia; 58% (11/19) of the pneumonias were bacterial, 37%(7/19) were fungal, and 5% (1/19) were protozol (Toxoplasma gondii). Twenty-seven percent of the bacterial pneumonias were due to Legionella. None of the patients had cytomegalovirus or P carinii pneumonia. Seven percent (7/10) of the study patients had fungal pneumonitis; 4% had invasive aspergillosis and 3% had cryptococcosis. Mortality was significantly higher (53%, 8/15) for patients with pneumonia than for patients without pneumonia (10%, 9/86,P=0.0004). Only fungal pneumonias were the direct cause of death; 63% (5/8) of the deaths were in patients with fungal pneumonitis. Our data suggest a changing pattern of microbial etiologies of pneumonitis in the era of modern immunosuppressive agents. We show that P carinii pneumonia and cytomegalovirus can be effectively curtailed with appropriate prophylaxis. Fungal infections, on the contrary, not only constituted a major proportion of the pneumonia, but also carried the highest pneumonia-associated mortality. Legionella infections can be over-looked unless specialized laboratory methodology (culture on selective media, urinary antigen) are applied routinely to all cases of pneumonia. We recommend routine culture of the water supply forLegionella in all transplant centers.