To assess the potential therapeutic use of three human monoclonal antibodies (MAbs) and one murine MAb, we tested the reactivity of these MAbs toward 100 clinical isolates of Pseudomonas aeruginosa. Seventy-five isolates were from hospitalized patients, while 25 were recovered from patients with documented cystic fibrosis. Nine isolates showed autoagglutination. The three human MAbs and one murine MAb exhibited agglutination with 81% of the P. aeruginosa isolates obtained from hospitalized patients and with 72% of the isolates from patients with cystic fibrosis. Eight of the autoagglutinating isolates were reactive in whole-cell ELISAs with the MAbs. The isolates recovered from patients with cystic fibrosis were reactive mainly with a MAb that is directed to the outer core of lipopolysaccharide (LPS); they showed hardly any reaction with O antigen-specific MAbs or typing sera, a finding indicating that these isolates lacked the O antigen and that the outer core of the LPS was still present. The reactivity of the MAb specific for the outer core of LPS toward P. aeruginosa isolates from patients with cystic fibrosis has potential value in eradicating P. aeruginosa from these patients.