The efficacy of amoxycillin–clavulanic acid (10 and 15 mg/kg amoxycillin) and erythromycin (20 and 50 mg/kg) was assessed in a gerbil model of otitis media with effusion induced by β-lactamase-producing Haemophilus influenzae. Animals were divided into groups receiving acetaminophen concomitantly or not receiving it. Treatment started 2 h post-middle ear inoculation and continued t.i.d. for up to three doses. Middle ear samples were obtained on day 2 post-inoculation. Amoxycillin–clavulanic acid showed significantly higher efficacy than erythromycin, regardless of acetaminophen administration ( P<0.05). Amoxycillin–clavulanic acid middle ear concentrations exceeded the amoxycillin MIC (1/0.5 μg/ml) by 1.88-fold, whereas erythromycin concentrations were below MIC level of 4 μg/ml. Animals receiving acetaminophen showed significantly fewer polymorphonuclear cells and more Haemophilus organisms in the middle ear exudate.