Endotoxins are potent pro-inflammatory substances present in several natural environments and in commercial house dust extracts. To investigate the possible effect of chronic endotoxin exposure on asthma, 28 patients with perennial chronic asthma (20 allergic to house dust mite and eight intrinsic asthmatics) were evaluated during a 4-month period (lung function, clinical and immunological criteria). At the same time, two house dust samples were collected from each patient's home to determine total house dust weight (mg/m2), endotoxin concentration and house dust mite antigen content (evaluated indirectly by guanine content with HPLC method). The mean (± s. d.) endotoxin concentration, as measured by quantitative Limulus assay was 2.59 (± 3.41) ng/mg house dust, ranging from 0.12 to 20 ng/mg. The mean guanine content was 0.13 (± 0.16) mg/100 mg house dust. There was no correlation between endotoxin and house dust mite concentrations. Patients were compared according to the low or high grade exposure to dust, endotoxins and guanine. Compared with patients with low grade (≤ 5.6 ng/ml) exposure, subjects exposed to high endotoxin concentrations (> 5.6 ng/ml) showed a significant increase in dyspnea (median 2.6 vs 3.3; P<0.05) and treatment (median 14 vs 44.3; P<0.01) scores, oral corticosteroid (median 0.0 vs 13.5 mg/24 hr; P<0.01) and β2-mimetics (median four vs eight puffs/day; P<0.01) intake, and a significant decrease in FEV1/FVC (median 84.5 vs 67% of predicted value; P<0.01). In contrast, no differences were found between the two groups exposed to low (< 0.07 mg/100 mg house dust) and high (≥ 0.07 mg/100 mg house dust) concentrations of guanine, respectively. We conclude that endotoxins are present in normal domestic environment and could have a deleterious effect on the chronic asthmatic disease.