Bovine herpesvirus-1 (BHV-1) is an important pathogen of respiratory infections in cattle. Its continuing importance lies in its ability to predispose infected hosts to bacterial infections (e.g., Pasteurella haemolytica). In this study we determined whether the immunoregulatory effects induced by recombinant bovine interleukin-1 (rbIL-1) could stimulate appropriate host defense mechanisms to influence the course of BHV-1 and P. haemolytica infection in cattle. We first evaluated the effect of multiple doses (5 doses of 300 ng/kg) of rbIL-1 in normal cattle. An increase in polymorphonuclear (PMN) cells, as well as monocytes, in peripheral blood was observed during the course of IL-1 administration. In addition, the phagocytic activity of monocytes was increased. Although the phagocytic and oxidative burst activities in PMN decreased during the course of rbIL-1 treatment, no changes were observed in the bactericidal capacity of these cells. Lymphocyte numbers in peripheral blood remained unchanged; however, the functional activity of these cells, as measured by IFN-gamma production upon in vitro stimulation, was decreased. In the bovine respiratory disease model, multiple administration of IL-1 did not influence significantly the progression of BHV-1/P. haemolytica infection in cattle. Thus, our results demonstrated that IL-1, although not therapeutically effective, could be administered safely as an adjuvant, even during the course of BHV-1/P. haemolytica infection.