SummaryOne hundred seventy six consecutive, non-duplicate pneumococcal isolates from clinical specimens collected from November 1994 through February 1995 in nine general hospitals throughout Belgium were tested for theirin vitrosusceptibilities to penicillin, ampicillin, amoxycillin with and without clavulanate, cefaclor, cefuroxime, cefonicid, cefprozil, cefpodoxime, cefotaxime, imipencm, tetracycline, and erythromycin by means of the NCCLS microdilution test. The overall rate of decreased susceptibility to penicillin was 12.5%, including 6.3% of intermediately and 6.3% of fully resistant isolates. Penicillin, ampicillin amoxycillin, amoxycillin/clavulanate, cefuroxime, cefotaxime and imipenem had the highest activity on a weight basis (MIC50<0.008 ng/ml), followed by cefpodoxime and erythromycin (MIC50 of 0.015 ng/ml), cefprozil and tetracycline (MIC50 of 0.12 ng/ml), and eventually, cefaclor and cefonicid (MIC50 of 0.5 ng/ml). Aggregate rates of susceptible plus intermediately resistant isolates at NCCLS-recommended breakpoints, i.e. overall percentages of isolates likely to respond to increased antibiotic dosesin vivo(except for meningitis), were 100.0% for imipencm and cefotaxime, 98.9% for amoxycillin with and without clavulanate, 93.8% for penicillin, and 90.9% for cefuroxime. Overall rates of susceptibility to erythromycin and tetracycline amounted to 78.4% and 72.7%, respectively. MIC values of all (i-lactams increased with those of penicillin. Ampicillin was equally active as penicillin against isolates with reduced susceptibility to the latter (MIC90 of 2 ng/ml); imipencm, cefotaxime, and amoxycillin with and without clavulanate however, were more active (MIC90 3, 1, and 1 doubling dilution, respectively, below that of penicillin), while cefpodoxime, cefuroxime, cefprozil, cefonicid, and cefaclor on the other hand, were less active (MIC90, 1, 1, 2, 5, and 5 doubling dilutions, respectively, above that of penicillin). In conclusion, the present data confirm that pneumococcal resistance to penicillin has increased in Belgium, suggest that resistance to erythromycin may have stabilised, and reveal an unexpectedly high rale of resistance to tetracycline. Imipencm was the most active antibiotic tested overall, and amoxycillin with or without clavulanate the most active oral antibiotic, with activity almost similar to that of cefotaxime.