In order to objectively document the accepted clinical efficacy of ampicillin in treating bacterial exacerbations of chronic bronchitis, as well as to evaluate the efficacy of methacycline, a double-blind crossover study was designed. Twenty patients with chronic bronchial disease were treated for two separate acute bacterial exacerbations, once with 2 gm of ampicillin daily, and once with 600 mg of methacycline daily, for 14 days. There were a few significant differences when comparing the efficacy of the antimicrobials. For example, the daily volume of sputum significantly went from 35.6 ml initially to 20.5 ml at the end of treatment with methacycline, and from 37.4 to 18.0 ml with ampicillin. Sputum neutrophils excreted per day went from 446 to 147 million with methacycline and from 433 to 94 million with ampicillin. Gram-positive diplococci and cocci on gram stains of sputum significantly decreased form 10.6 to 3.3 with methacycline and from 16.8 to 2.1 with ampicillin. This investigation objectively documents with accepted clinical efficacy of ampicillin and proves methacycline to be an equally effective agent.