The objective of this study was to investigate whether treatment with single-dose dexamethasone can provide relief of symptoms in acute exudative pharyngitis. A prospective, randomized, double-blinded, placebo-controlled clinical trial was undertaken over a 3-month period in a university-based Emergency Department. The study included all consecutive patients between 18 and 65 years of age presenting with acute exudative pharyngitis, sore throat, odynophagia, or a combination, and with more than two Centor criteria. Each patient was empirically treated with azithromycin and paracetamol for 3 days. The effects of placebo and a fixed single dose (8 mg) of intramuscular injection of dexamethasone were compared. The patients were asked to report the exact time to onset of pain relief and time to complete relief of pain. After completion of the treatment, telephone follow-up regarding the relief of pain was conducted. A total of 103 patients were enrolled. Thirty patients with a history of recent antibiotic use, pregnancy, those who were elderly (>65 years of age) and patients who failed to give informed consent were excluded. Forty-two patients were assigned to the placebo group and 31 were assigned to the intramuscular dexamethasone group (8-mg single dose). Time to perceived onset of pain relief was 8.06+/-4.86 h in steroid-treated patients, as opposed to 19.90+/-9.39 h in the control group (p=0.000). The interval required to become pain-free was 28.97+/-12.00 h in the dexamethasone group, vs. 53.74+/-16.23 h in the placebo group (p=0.000). No significant difference was observed in vital signs between the regimens. No side effects and no new complaints attributable to the dexamethasone and azithromycin were observed. Sore throat and odynophagia in patients with acute exudative pharyngitis may respond better to treatment with an 8-mg single dose of intramuscular dexamethasone accompanied by an antibiotic regimen than to antibiotics alone.