Resistance of Streptococcus pneumoniae to antimicrobial agents shows geographical variation and also depends on serotype, patient age and sample origin. Factors affecting antibiotic resistance in S. pneumoniae were studied from results of a multicentre susceptibility study of 12 antimicrobial agents, carried out in 14 Spanish hospitals between May 1996 and April 1997. The most frequent serotypes were serotypes 6 (14.8%), 19 (11.8%), 23 (10.5%), 3 (9.9%), 9 (8.0%), 14 (8.0%), 15 (3.9%) and 11 (3.2%); 9.6% of isolates were not typeable. The remaining 25 serotypes constituted 20.2% of strains. Penicillin resistance was more prevalent in serotypes 14 (88%), 23 (66%), 9 (62%) and 6 (57%), whereas erythromycin resistance was more prevalent in serotypes 6 (68.5%), 15 (61.4%), 14 (49.5%), 19 (42.7%) and 23 (39.3%). Serotypes 6 and 19 were the serotypes most commonly isolated from both children and adults, although with different proportions (24.0% and 19.2% of isolates from children were serotype 6 and 19, respectively, with the corresponding figures for isolates from adults being 13.6% and 11.5%, respectively). The rates of resistance of pneumococcal strains to penicillin and cefuroxime were significantly higher in strains from children than in those from adults (resistance to penicillin, 50.4% in children and 37.0% in adults; resistance to cefuroxime, 62.4% in children and 45.6% in adults). There was significantly more resistance to erythromycin in middle ear isolates (48.9%) than in blood isolates (27%). The prevalence of resistance to beta-lactams showed a seasonal pattern, with higher rates in summer and winter, proportional to the magnitude of resistance. Susceptibility to macrolides did not vary seasonally. Our results stress the relative importance that geographical, temporal (seasonality), patient (sample type, origin, age group) and bacterium-related (serotype) factors have on the variations in susceptibility observed among different pneumococcal clinical isolates.