The antimicrobial susceptibility profile of 77 oropharyngeal viridans streptococci isolates from 34 cystic fibrosis (CF) patients and 58 isolates from 43 healthy non-CF patients were studied by the E-test and the standard disk diffusion methods. Overall penicillin and cefotaxime resistances (intermediate plus resistant isolates) were significantly higher (p < 0.05) among CF isolates (72.7% and 45.5%, respectively) than among non-CF isolates (51.7% and 15.5%, respectively). No significant difference was observed in overall (intermediate plus resistant) erythromycin resistance rates, although high-level erythromycin resistance (> or =32 microg/mL) was more frequently found in CF isolates (24.6%) than in non-CF isolates (12.1%). An unexpected high percentage of isolates showed low level erythromycin resistance (MIC range, 0.5-15 microg/mL): 41.5% in cystic fibrosis and 46.5% in non-CF isolates. No significant differences were observed regarding the percentage of colonized patients with at least one penicillin-resistant isolate. On the contrary, colonization with cefotaxime (p < 0.001) or erythromycin (p = 0.014) resistant isolates were significantly more prevalent in CF patients. Similar tetracycline and chloramphenicol resistance rates were observed for both groups. Viridans isolates resistant to a single antibiotic were more prevalent among non-CF patients and multiple resistance was higher among CF patients. Prior antibiotic exposure could result in differences in beta-lactam resistance and colonization rates with resistant isolates between both groups. None of the non-CF patients was previously treated with antimicrobials for a period of three months before sampling. In contrast, 94.1% of CF patients were treated with antimicrobials within the same period; 65.6% with beta-lactam antibiotics. Patients with CF disease, frequently exposed to antimicrobials, may be a reservoir of viridans streptococci isolates with resistance determinants, particularly to beta-lactam antibiotics.