This paper presents data relating to Haemophilus influenzae and Moraxella catarrhalis from PROTEKT (1999-2000), a surveillance study that examined the susceptibility of respiratory pathogens to current and new antibacterials. Beta-lactamase production is the principal mechanism of resistance to ampicillin and other beta-lactam antibacterials in H. influenzae and M. catarrhalis. The PROTEKT study showed that globally, the prevalence of beta-lactamase production in H. influenzae varied considerably: of 2948 isolates, 489 (16.6%) were beta-lactamase-positive [range: 1.8% (Italy) to 65% (South Korea)]. Beta-lactamase-negative, ampicillin-resistant (BLNAR) strains of H. influenzae were uncommon (<0.1%) but their very detection highlights the need for continued vigilance. Overall, few isolates of H. influenzae showed resistance to either macrolides or telithromycin. The emergence of clarithromycin-resistant strains is worrying, however, as such isolates may also show resistance to other macrolides. There was a geographical correlation between beta-lactamase production and the prevalence of resistance to chloramphenicol and tetracycline among the H. influenzae isolates. Of 1131 M. catarrhalis isolates, 92% were beta-lactamase-positive. Most isolates, however, were fully susceptible to nearly all the antibacterials tested, except ampicillin. The most active were ciprofloxacin and levofloxacin (both having MIC(90) values of 0.03 mg/L), moxifloxacin (MIC(90) 0.06 mg/L), azithromycin (MIC(90) < or = 0.06 mg/L) and telithromycin (MIC(90) 0.12 mg/L). Overall, there were no concerns in terms of resistance to fluoroquinolones for both H. influenzae and M. catarrhalis. In summary, the PROTEKT surveillance study confirmed the problem of widespread prevalence of beta-lactamase-producing strains of H. influenzae and M. catarrhalis, although these pathogens generally remain susceptible to macrolides, fluoroquinolones and the new ketolide telithromycin.