The antimicrobial resistance of Streptococcus pneumoniae was surveyed in 1970-1990 at Saint Joseph and Broussais hospitals in Paris (3,279 isolates) and in 1984-1990 at the National Reference Center for Pneumococci (NRCP) in Créteil (8,128 isolates). All isolates were tested for susceptibility and serotyped. At St. Joseph and Broussais hospitals, the rate of resistance to tetracycline increased from 14% in 1970 to 46.5% in 1978 and then decreased to approximately 20% in 1988-1990. Resistance to chloramphenicol appeared in 1972; its frequency remained at less than 10% until 1990. Resistance to macrolides was first detected in 1976, increased to 20% in 1984, and reached 29% in 1990. Among strains submitted to the NRCP, resistance to penicillin (MIC, greater than or equal to 0.1 mg/L) remained infrequent (less than or equal to 1.1%) between 1984 and 1986 but then increased steadily, reaching 12% in 1990. The frequency of high-level resistance to penicillin (MIC, greater than 1 mg/L) among penicillin-resistant pneumococci increased from 13% in 1988 to 48% in 1990. Compared with other serotypes, the penicillin-resistant serotype isolated most frequently (23F, 49.3%) was more often highly resistant to penicillin and was more often multiresistant.