OBJECTIVES: The aim of the study was to evaluate the antibiotic resistance in noninvasive clinical isolates of Streptococcus pneumoniae collected in Belgium during winter 2008-2007. METHOD: Four hundred and forty eight unduplicated isolates collected by 15 laboratories were tested by microdilution following CLSI. RESULTS: Insusceptibility rates (I+R) were as follows: penicillin G (PEN) 11.6% (4.0% R), ampicillin 11.4% (4.0% R), amoxicillin+/-clavulanic acid 0, cefaclor 10.3% (9.6% R), cefuroxime 9.2% (8.7% R), cefuroxime-axetil 8.7% (7.8% R), cefotaxime, ceftazidime and cefepime 2.0% (0% R), imipenem 2.5% (0% R), ciprofloxacin and ofloxacin 5.1% (0.4% R), levofloxacin 0.7% (0.4% R), moxifloxacin 0.4% (0.2% R), erythromycin (ERY) 29.7% (29.2% R), azithromycin 29.7% (28.8% R), telithromycin 0%, clindamycin 26.3% (25.4% R) and tetracycline (TET) 21.9% (16.5% R). From 2001 to 2008, a significant decrease in penicillin-insusceptibility (21.0% to 11.6%), penicillin-resistance (9.7% to 4.0%) and ciprofloxacin-insusceptibility (11.2% to 5.1%) was found. Cross-resistance between penicillin and other betalactams in penicillin-insusceptible isolates was incomplete: all these isolates remained fully susceptible to amoxicillin. Erythromycin-insusceptibility was significantly higher in children than in adults (43.9%/27.4%), while penicillin-insusceptibility significantly higher in Brussels than in the Flanders (22.9%/8.1%). The commonest resistance phenotype was ERY-TET (12.7%) followed by ERY (7.4%) and PEN-ERY-TET (5.8%). Capsular types 19 (25%), 14 (19.3%), 23 (15.4%) and 15 (13.5%) were the most important in penicillin-insusceptible. CONCLUSION: We noted a decrease in resistance to the majority of the compounds. Insusceptibility rates were higher in children than in adults and the difference between the north and the south of Belgium became less marked