The resistance pattern of 105 consecutive strains of Streptococcus pneumoniae isolated from patients at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia over a 2-year period (March 1998 to February 2000) was determined with the minimal inhibitory concentration (MIC) method using E-test. Overall 6.7% of the isolates were penicillin resistant (MICs greater than or equal to2 mg/L), and 51% were intermediate (MICs 0.12 - I. mg/L), The resistance rates to ampicillin, cefotaxime, ceftriaxone, imipenem, erythromycin and clarithromycin were 8.6%, 8.6%, 4.7%, 3.8%, 13%, and 21% respectively. High-level resistance was noted against cotrimoxazole and chloramphenicol, 76% and 68% respectively. Only 2.8% of S. pneumoniae were resistant to amoxycillin-clavulanate; no resistance to vancomycin was observed. Against penicillin-intermediate pneumococcal strains, vancomycin, ceftriaxone, cefotaxime and amoxycillin-clavulanate were the most active compounds. Against penicillin-resistant pneumococci, vancomycin was the most powerful agent, amoxyciIlin-clavulanate was half as active, whereas ceftriaxone, cefotaxime and imipenem were 4-fold less active than vancomycin, Fifty-six (53%) of the 105 pneumococcal strains were multi-drug resistant.