During the 13-year period from 1 November 1980 to 31 January 1993, we received and serotyped a total of 5,619 clinically significant strains of Streptococcus pneumoniae isolated in more than 75 laboratories in Belgium (4,079 [72.6%] were from blood or pleural fluid, 462 [8.2%] were from cerebrospinal fluid, 691 [12.3%] were from middle ear aspirates, and 387 [6.8%] were from various other body fluids). The isolates belonged to 64 of the 84 currently recognized serotypes. Among the 4,722 isolates tested for susceptibility since 1983, 22% were resistant to at least one antimicrobial agent. Resistance to penicillin has slowly increased since 1985 but remained stable at a level of 2%–4% between 1986 and 1993. Of the 119 isolates with reduced penicillin susceptibility, only 23 were fully resistant (MIC, ⩾2 µg/mL) and none of these proved to be resistant to cephalosporins. Resistance to erythromycin increased significantly from 5.2% in 1986 to 21.5% in 1993. Resistance to penicillin and erythromycin was also more frequently recognized in a smaller number of capsular types of S. pneumoniae .