Antimicrobial resistance of Streptococcus pneumoniae and Haemophilus influenzae presents a challenge to clinical case management, particularly in programs for acute respiratory tract infection (ARI), including pneumonia, in developing countries. To determine whether nasopharyngeal isolates of S. pneumoniae and H. influenzae from a clinically defined group of children could be used to predict the prevalence of antimicrobial resistance of strains that cause disease, 601 urban children with ARI, 133 healthy urban children and 285 rural children were evaluated in Pakistan. Of the urban children with ARI, 216 (35.9%) were bacteremic, predominantly with S. pneumoniae (108 children) and H. influenzae (100 children). Overall 631 (61.9%) children carried S. pneumoniae and 381 (37.4%) carried H. influenzae. The proportions of nasopharyngeal isolates of both organisms from urban children with ARI resistant to penicillin or ampicillin, trimethoprim/sulfamethoxazole, chloramphenicol and erythromycin were similar to the proportions of resistant blood isolates. Nasopharyngeal isolates from rural children had lower rates of resistance to some antimicrobial agents. These findings suggest that nasopharyngeal isolates of S. pneumoniae and H. influenzae from children with ARI can be used to conduct surveillance for antimicrobial resistance in a defined geographic area. Such surveillance would aid programs in developing countries in making a rational choice of antimicrobial agents for use in clinical management of bacterial diseases, including pneumonia.