We have evaluated the effect of intraperitoneal (I.P.) injection of human recombinant interferon-2alpha (IFN-alpha) on Bleomycin-induced pulmonary injury in hamsters. Pulmonary injury was induced by a single intratracheal (I.T.) instillation of Bleomycin (Bleo). Six groups of male Syrian hamsters were treated as follows: 1) I.T. Bleo and daily I.P. injections of low-dose interferon-alpha (2 x 10(4) U), 2) I.T. Bleo and daily I.P. injections of high-dose interferon-alpha (10(5) U), 3) I.T. Bleo and I.P. injections of saline, 4) I.T. saline and I.P. low-dose IFN-alpha, 5) I.T. saline and I.P. high-dose IFN-alpha, 6) I.T. saline and I.P. saline. Animals were sacrificed 28 days after I.T. treatment. Lung injury was evaluated histologically and biochemically. Treatment of hamsters with low-dose but not high-dose IFN-alpha significantly augmented the Bleo-induced lung injury, as determined by a semiquantitative morphological index. Lung hydroxyproline measurements were highest in Bleo-low-dose-IFN-alpha followed by Bleo-high-dose-IFN-alpha and Bleo-Sal as compared to Sal-Sal and Sal-IFN-alpha controls. These results suggest that IFN-alpha augments Bleo-induced lung injury but that this effect is complex and does not follow a simple-dose-response pattern.