This study tested 212 pneumococcal isolates from 9 institutions for their susceptibilities to penicillin, ampicillin, amoxycillin, amoxycillin/clavulanate, cefaclor, cefuroxime, cefotaxime, imipenem, tetracycline, erythromycin, and clarithromycin using NCCLS-standardized microdilution. Penicillin-insusceptibility was 12.3% [5.7% intermediate (0.12-1 microgram/ml) and 6.6% high-level (> or = 2 micrograms/ml)], tetracycline-insusceptibility (> or = 4 micrograms/ml) 31.1%, and erythromycin-insusceptibility (> or = 0.5 microgram/ml) 31.1% as well. Erythromycin-insusceptible isolates showed cross-insusceptibility to clarithromycin. Penicillin-susceptible isolates were susceptible to all beta-lactams. MICs of all beta-lactams rose with those of penicillin for penicillin-insusceptible isolates. Ampicillin and penicillin were equally potent against penicillin-insusceptible isolates, imipenem, cefotaxime, and amoxycillin +/- clavulanate were more potent (generally 5, 1, and 1 doubling dilution, respectively), and cefuroxime and cefaclor less potent (generally 1 and 6 doubling dilutions, respectively). Most penicillin-insusceptible isolates were high-level resistant to cefaclor (> or = 32 micrograms/ml). Although MICs of all beta-lactams rose with those of penicillin, resistance to penicillin was not absolute in terms of cross-resistance. Most penicillin-intermediate and high-level penicillin-resistant isolates remained fully susceptible and intermediate, respectively, to amoxycillin +/- clavulanate, cefotaxime, and imipenem, but not to cefuroxime. Penicillin-susceptible isolates were 76.9%, 42.3%, and 34.6% co-insusceptible to tetracycline, erythromycin, and tetracycline plus erythromycin, respectively. Most penicillin-, tetracycline-, and erythromycin-insusceptible isolates were of capsular types 23 >> 6 > 19 > 32, 19 > 6 > 28 > 23, and 19 > 6 > 14 > 23, respectively. Compared to winter 1994-1995, insusceptibility to penicillin, tetracycline, and erythromycin rose by some 4%, 4%, and 13%, respectively.