A total of 278 alpha- and nonhemolytic streptococcal isolates (patients, n = 116; healthy adults, n = 162) were examined for susceptibility to 23 and 24 antimicrobial drugs with the Bauer-Kirby agar disk diffusion and the agar dilution method, respectively. Wilkins-Chalgren medium compared favorably with sheep blood Mueller-Hinton agar, the reference medium, for 58 representative streptococcal isolates. In terms of minimal inhibitory concentrations (MICs), all 278 isolates were susceptible to teicoplanin and vancomycin. None of the isolates revealed high-level gentamicin resistance. All isolates were resistant to fusidic acid. Twelve Streptococcus mitis isolates, all from patients, were resistant to penicillin G and variably to other antibiotics. Oxacillin disks failed to predict penicillin G susceptibility. In general, patient isolates were more frequently resistant to beta-lactam antibiotics and fluoroquinolones; conversely, isolates from healthy carriers were slightly more resistant to macrolide antibiotics. Specifically, susceptibility rates were: penicillin G 79.1%, oxacillin 87.8%, ampicillin 66.9%, piperacillin 98.2%, cefoxitin 76.6%, cefuroxime 96.8%, cefotaxime 98.6%, ceftriaxone 98.6%, cefepime 98.6%, impipenem 98.2%, ciprofloxacin 59.7%, ofloxacin 89.2%, doxycycline 65.8%, tetracycline 56.8%, clindamycin 87.8%, erythromycin 59%, clarithromycin 74.9%, chloramphenicol 98.9%, cotrimoxazole 97.9%, rifampin 97.5%, and fosfomycin 2.2%. On the basis of numerous minor discrepancies between disk diffusion and agar dilution test results for certain antibiotics, it is proposed that the current NCCLS inhibition zone (diameter, mm) criteria indicative of intermediate susceptibility of alpha- and nonhemolytic streptococci be changed for the following antimicrobial drugs: ampicillin = I = 22-27 mm; ciprofloxacin = I = 16-18 mm; clindamycin = I = 15-18 mm; doxycycline = I = 17-19 mm; tetracycline = I = 17-19 mm; erythromycin = I = 14-19 mm, and cotrimoxazole = I = 11-13 mm. It is recommended to exclude both cefoxitin and doxycycline (substitute = tetracycline) disks from test batteries for non-group A, B beta-hemolytic and alpha-/nonhemolytic streptococcal isolates.