Serotypes and antibiotic susceptibilities were determined for 2,197 Streptococcus pneumoniae strains isolated from patients with systemic infections over an 11-year period. The predominant serogroups and serotypes, in order of decreasing frequency, were 3, 6, 23, 19, 9, 1, 5, 8, 7, 14, 4, and 15; these types accounted for more than 75% of the strains studied. Altogether, 93% of the pneumococci belonged to groups or types included in the 23-valent pneumococcal vaccine. Overall, 65.5% of pneumococci were resistant to one or more drugs. The incidence of penicillin-resistant pneumococci rose from 6% in 1979 to 44% in 1989, and the degree of penicillin resistance also increased throughout the study. Overall, the resistance rates were 28% for penicillin, 56% for tetracycline, 43% for chloramphenicol, and 5% for erythromycin. Seventy-one pneumococcal isolates resistant to all four antibiotics tested were found. The prevalence of pneumococcal resistance in Spain is, as far as we know, among the highest published to date.