Immunoglobulin G (IgG) antibodies to Pseudomonas aeruginosa surface antigens in serum were estimated by enzyme-linked immunosorbent assay for all patients from whom P. aeruginosa was isolated for the first time during a study period of 3 years (33 patients). The titer of IgG antibodies was greater than control values at or up to 24 months before the first isolation of P. aeruginosa in 24 patients. Another five patients had titers that were within the control range before isolation of P. aeruginosa but increased to above the control range within the following 2 months. In these 29 patients, continuing intermittent isolations of P. aeruginosa were accompanied by further increases in titer. The presence of a systemic immune response above the control range indicates tissue invasion and hence infection. Four patients were deemed to have no infection: one or two isolations of P. aeruginosa were accompanied by no increase in specific antibodies to above the control range throughout the entire study period. Fifteen patients received intravenous antipseudomonal chemotherapy. Eradication of the organism and a return of titer to control values, suggesting complete removal of the organisms, occurred in 5 patients, while continued isolations and only a partial decrease in titer occurred in 10 patients. The 15 patients who received treatment improved clinically, in contrast to untreated patients, whose clinical state worsened during the study period. Continuous steroid treatment, given to two patients, was accompanied by a dramatic decrease in both serum IgG concentration and titer, despite continuing intermittent isolations of P. aeruginosa. These results confirm and extend our earlier finding that this assay appears to detect P. aeruginosa infection at a very early stage and helps in differentiating between early infection and harmless colonization. It also appears to be a useful monitor of the progress of infection and the response to intravenous antibiotic treatment in these early stages of infection, before any clinical changes are sufficiently large to be detected, in patients who were not on continuous steroid therapy. The effect of steroid treatment on the immunological response and clinical outcome of patients with early P. aeruginosa infection requires further investigation.