Bacterial extracts can act as immune stimulants and in some instances have been used, rather empirically, to prevent recurrent infections in the nonimmunocompromised host. Some agents are administered via oral route with the goal to increase airways immune defenses. In animal models and in normal humans, gut-associated lymphoid tissue (GALT) stimulation is able to induce a generalized response by the whole mucosal-associated lymphoid tissue (MALT). The aim of this placebo-controlled, double-blind, parallel-group study was to evaluate whether the stimulation of the GALT through oral administration of a polyvalent bacterial extract (BE) could lead to significant immune modifications either systemically or locally in the respiratory tract in patients suffering from chronic bronchitis. We selected 20 subjects (5 nonsmokers, 6 smokers, and 9 ex-smokers) for at least 3 years. According to a balanced-block randomization method, ten patients received active treatment and ten received placebo. Either drug or placebo was to be taken as one capsule daily the first 10 days of 3 consecutive months. Each capsule of the active product contained 7 mg of a BE obtained from eight different bacterial strains. On entry (T0) and 90 days after beginning of treatment (T90), all patients underwent bronchoalveolar lavage (BAL) and peripheral blood withdrawal to assay BAL fluids and serum samples for immune parameters. The BAL recoveries, cellularity, cell differentials, and lymphocyte subsets (CD19, CD3, CD4, CD8) did not show significant differences. IgG/albumin and IgA/albumin values were not significantly different, but IgA/albumin was significantly increased in the treatment (T0 = 0.14, 0.01 to 0.27, median and range, T90 = 0.15, 0.08 to 0.45, p = 0.028) vs the placebo group when data from current smokers were excluded. Functional tests on alveolar macrophages (AM) (leading front stimulated motility and superoxide anion-O2(-)-release) showed a significant increase of random migration (T0 = 10.6, 7.0 to 23.6, T90 = 13.4, 8.1 to 28.8 microns, p = 0.02) and of stimulated motility after FMLP 10(-7) M (T0 = 13.2, 8.3 to 46.4, T90 = 18.3, 8.4 to 49.6 microns, p = 0.04), a significant increase of O2- release in basal conditions (T0 = 6.0, 1.7 to 30.5 nM/10(6) AM/10', T90 = 11.1, 5.5 to 24.5, p = 0.05) and after stimulation with opsonized zymosan (T0 = 17.7, 4.7 to 35.2, T90 = 22.1, 13.8 to 53.3, p = 0.009) in the treatment group only. Data were not significantly different in the placebo group between T0 and T90. No modifications in systemic immunity were ever observed.(ABSTRACT TRUNCATED AT 400 WORDS)