BACKGROUND: Community-acquired pneumonia is a major cause of death in third world countries. Antimicrobial therapy may have little impact on the natural history of patients with severe pneumonia. We hypothesized that the intrapulmonary production of tumor necrosis factor-alpha (TNF-alpha) may be responsible for the progressive lung injury and shock commonly seen in patients with severe pneumonia after commencing antibiotic therapy. AIM: To investigate the effects of a single bolus of hydrocortisone on the clinical course and serum TNF-alpha levels of patients with severe community-acquired pneumonia. DESIGN: Randomized placebo-controlled study. SETTING: Multidisciplinary ICU of a tertiary care teaching hospital. PATIENTS AND METHODS: Patients with three or more British Thoracic Society criteria of severe pneumonia were studied. Patients were randomized to receive either a single dose of hydrocortisone (10 mg/kg) or placebo 30 min prior to commencing antibiotic therapy. Patients were treated with cefotaxime and other antibiotics as clinically indicated. Blood for TNF-alpha was taken at the time of hospital admission and repeated 2, 6, and 12 h after starting antibiotic therapy. RESULTS: Thirty patients were studied: 16 received placebo and 14 received hydrocortisone. The patients who received placebo tended to be sicker than the patients who received hydrocortisone. The baseline TNF-alpha value was 989 +/- 374 pg/ml in the placebo group and 827 +/- 394 pg/ml in the hydrocortisone group. In both groups of patients, the TNF-alpha levels did not change significantly with time. There was no correlation between the TNF-alpha levels and the APACHE II score, lung injury score, or outcome. The only variable that predicted outcome was the APACHE II score. CONCLUSION: Bactericidal antibiotics do not increase serum TNF-alpha levels in patients with severe pneumonia. Hydrocortisone given prior to antibiotic treatment had no effect on the serum TNF-alpha levels or the clinical course of patients with severe community-acquired pneumonia.