Objectives: The study compared nasopharyngeal carriage of resistant pneumoniae in human immunodeficiency virus (HIV)-seropositive and -seronegative children., Methods: Nasopharyngeal colonization with Streptococcus pneumoniae was investigated during May 1996 in 162 HIV-negative infants and children (age range, 1-38 mo) and 40 HIV-infected children (age range, 39-106 mo) living in an orphanage in Iasi, northeastern Romania. The HIV-infected children lived separated from the other children and were cared for by a different staff. Streptococcus pneumoniae was isolated from 12 of 40 (30%) HIV-infected and from 81 of 160 (50%) HIV-negative children. Antimicrobial susceptibility to penicillin and ceftriaxone was determined by E-test, and to another five antibiotics by disk diffusion. Serotyping was performed by the Quellung method on 81 of 93 (87%) isolates., Results: Serotypes 6A, 6B, 19A, and 23F together represented 98% of all isolates. Ninety-nine percent of S. pneumoniae isolates were resistant to penicillin, and 74% were highly resistant to penicillin (minimum inhibitory concentration [MIC] > 1 mg/mL); MIC50 and MIC90 to penicillin of the isolates were 2 mg/mL and 8 mg/mL, respectively. Eighty-nine of ninety-one isolates were susceptible to ceftriaxone; 99%, 87%, 87%, 48%, and 21% of the isolates were resistant to trimethoprim-sulphamethoxazole, erythromycin, clindamycin, tetracycline, and chloramphenicol, respectively. Eighty-two (89%) isolates were multidrug resistant (resistant to =/>3 antibiotic classes); 37 of 92 (40%) isolates were resistant to 5 or more antibiotic classes, and 16 of these 37 (43%) belonged to serotype 19A. All serotype 19 isolates were highly resistant to penicillin., Conclusions: No significant differences were observed in the resistance rates of S. pneumoniae in HIV-infected children compared to HIV-negative children. Multidrug-resistant pneumococci were highly prevalent in this Romanian orphanage in both HIV-negative and older HIV-infected children. The observed high prevalence of multidrug-resistant pneumococci (coupled with high penicillin resistance) with a limited number of circulating serotypes emphasizes the need to further evaluate the conjugate vaccines in children at risk for invasive pneumococcal infection.