BACKGROUND: Acute cough with purulent sputum is a common complaint presented to general practitioners. AIM: A randomized, double blind, placebo controlled clinical trial was undertaken to determine the efficacy of doxycycline in persons aged 18 years and over presenting to 22 general practices in the Netherlands with acute cough and purulent sputum. METHOD: Patients were excluded if they were pregnant, had an allergy or intolerance to tetracyclines, had severe dyspnoea and fine crackles on auscultation, purulent rhinitis together with maxillary tenderness, chronic airways disease, or had taken antibiotics in the previous two weeks. Patients entered in to the study were given oral doxycycline for 10 days, 200 mg on the first day, followed by 100 mg on the next nine days, or placebo. RESULTS: Duration of frequent daytime cough after entry was a mean of 1.5 days shorter in the group of 71 patients receiving doxycycline than in the group of 69 patients on placebo (4.7 days versus 6.2 days, respectively). In patients aged 55 years and over the mean duration of frequent day-time cough after entry was 4.1 days shorter in the group taking doxycycline than in the placebo group. Patients with a very frequent cough and who also felt ill at entry regained their normal daily activities 2.1 days earlier when using doxycycline than the control group. CONCLUSION: Doxycycline has small beneficial effects in patients with acute cough and purulent sputum. These beneficial effects are more prominent, and probably clinically relevant, in patients aged 55 years and over and in patients who cough very frequently and who also feel ill.