Helicobacter pylori infection has proven to be extraordinarily difficult to eradicate. Antimicrobial monotherapies have been particularly disappointing, with most eradication rates in the range of 0 to 15%. We evaluated cefprozil (250 mg q.d.s. for 14 days) in 12 H. pylori-infected subjects. The 13C-urea breath test was used to evaluate effectiveness of therapy. Eradication was defined as a negative urea breath test 4 to 6 weeks after the end of treatment. Suppression of H. pylori was demonstrated in 4 of 12 (33%) by a negative urea breath test two days after start of treatment. H. pylori infection was not eradicated in any subject (0%). Adverse events were intermittent and mild. Cefprozil does not appear to offer promise as monotherapy for the eradication of H. pylori.