In this study the protection afforded against aerosolized Yersinia pestis by injection of an alhydrogel-adsorbed bed sub-unit vaccine has been compared with that given by an existing killed whole cell vaccine licensed for human use, The sub-unit vaccine protected mice against exposure to > 10(4) colony-forming units (c.f.u.) of virulent plague organisms (100 LD50 doses), whereas the whole cell vaccine provided only 50% protection against 1.8 x 10(3) c.f.u. In subunit vaccinees, IgG to each of the F1 and y antigens contained in the vaccine, was detected in serum, on direct secretion by spleen cells and in broncho-alveolar washings (BAL). In killed whole cell vaccinees, physiologically significant levels of Ige to Fl only were detectable inequivalent samples. Levels of F1-specific Ige in serum, secreted from spleen cells and in BAL were significantly higher (P < 0.01) in sub-unit compared with killed whole cell vaccinees. IgA was not detected in BAL from intra-muscularly nosed sub-unit vaccinees and thus the protection achieved against inhalational challenge with Yersinia pestis is attributed to the induction of systemic immunity to both the F1 and V antigens in the sub-unit vaccine, The enhanced protective efficacy of this sub-unit vaccine over an existing vaccine has been demonstrated in all animal model of pneumonic plague. (C) 1997 Elsevier Science Ltd.