In 1992, an ongoing, international multicenter study was established to investigate the antimicrobial susceptibility of community-acquired lower respiratory tract bacterial pathogens: the Alexander Project. Isolates cultured from patients living in geographically separated areas, ten in the European Union (EU) and five in the United States (US), were collected and tested using standard methods in a central laboratory. A total of 4,155 isolates of Haemophilus influenzae was collected during the period 1992-1994. beta-lactamase production was the principal mechanism of resistance observed with overall rates in the US (1992 = 26.3%; 1993 = 28.2%; and 1994 = 30.1%) generally twice those seen in the EU (1992 = 12.3%; 1993 = 14.4%; and 1994 = 15.5%). Chloramphenicol resistance was generally low except in Spanish centers where rates ranging from 4.0 to 15.9% were observed during the study period. One thousand one hundred ninety-three isolates of Moraxella catarrhalis were tested. beta-lactamase production was the only mechanism of resistance of any importance detected, with the vast majority of isolates producing the enzyme. Two thousand eight hundred twenty-nine isolates of Streptococcus pneumoniae were tested. French and Spanish centers provided isolates with the highest rates of either low-level (intermediate) or high-level penicillin resistance, which in 1994 ranged from 10.2 to 31.4% and 30.4 to 40.1% for each resistance category, respectively. With the exception of the fluoroquinolones, rates of resistance to other antimicrobials including the macrolides, doxycycline, chloramphenicol, and trimethoprim/sulfamethoxazole were high, generally, in centers with a high prevalence of penicillin resistance. However, in some centers (Toulouse, France and Genoa, Italy) this association was not complete for the macrolides.