Haemophilus influenzae was isolated from patients with respiratory tract infections in five centers in Saudi Arabia. All of the 129 isolates tested by MIC agar dilution were fully susceptible to ceftazidime and ciprofloxacin but 13.2% were resistant to ampicillin, 7% to tetracycline, 5.4% to chloramphenicol, 3.9% to roxithromycin, and 1.6% to amoxicillin/clavulanic acid. Seventeen (13.2%) of all isolates produced TEM-1 type beta-lactamase, the majority (82%) characterized as biotype I or II with 4 (23.5%) encapsulated and belonging to serotype b. There was a clear distinction between the prevalence of beta-lactamase production in hospital patients (26.3% of 19 isolates) compared with community based patients (10.9% of 110 isolates). In addition, we report an increase in the prevalence of beta-lactamase negative, ampicillin intermediate strains (BLNAI) compared to previous studies in this defined geographical region. Changes in the frequency and nature of antimicrobial resistance in common respiratory pathogens confirms the need to maintain surveillance.