Rates of antimicrobial resistance have been increasing in bacteria responsible for community-acquired lower respiratory tract infections in the United States. Nearly 100% of clinical isolates of Moraxella catarrhalis now produce beta-lactamase, an enzyme that renders this pathogen resistant to such agents as penicillin, ampicillin, and amoxicillin. However, this organism remains nearly uniformly susceptible to alternative oral antimicrobials, such as cephalosporins, macrolides, tetracyclines, beta-lactamase inhibitor combinations, and the combination of trimethoprim/sulfamethoxazole. The susceptibility of M. catarrhalis to these agents is not expected to change markedly in the next few years. A linear increase in the prevalence of beta-lactamase-mediated ampicillin resistance has been evident among isolates of nontypeable Haemophilus influenzae during the past decade in the United States. By the year 2000, 45-50% of isolates are likely to produce beta-lactamase. Although the susceptibility of this organism to alternative oral antimicrobials varies, rates of resistance to cefuroxime axetil, cefpodoxime, cefixime, azithromycin, and perhaps clarithromycin remain < 1%. The rate of penicillin resistance among isolates of Streptococcus pneumoniae, which has increased steadily in recent years, currently stands at approximately 25% in the United States and will likely reach 40-50% during the next 5-10 years. Because of cross-resistance, in general all beta-lactam antimicrobials have reduced activity against penicillin-resistant strains of S. pneumoniae. A 1994-1995 survey found that 3.4% of S. pneumoniae isolates were highly resistant to cefotaxime, and 4-8% were resistant to chloramphenicol, tetracycline, and the macrolides. Resistance to these antimicrobials has usually followed the emergence of penicillin resistance in other countries. Therefore, S. pneumoniae resistance to these drugs is expected to increase markedly during the next few years in the United States.