In 1998 we conducted a multicentre study in Spain on the susceptibility of Streptococcus pyogenes isolates to different 14-, 15- and 16-membered macrolides and clindamycin, in which the number of strains examined was proportional to the number of inhabitants in each geographical area. The aim of the present work was to re-examine the antimicrobial susceptibility of S. pyogenes in 2001, using the same methodology and centres as in 1998, to determine the different susceptibility phenotypes to macrolides-lincosamides, and to compare the results from the 2 years by statistical tests. A total of 529 unique isolates of S. pyogenes, collected in 21 laboratories, were studied. Throat swabs provided 417 isolates (78.8%), and the remaining 112 were from other sources. Four hundred and thirty-five (82.2%) were isolated from children and 94 (17.8%) from adults. One hundred and fifty-seven (29.7%) of the isolates were resistant to erythromycin and azithromycin, whereas resistance to miocamycin, a 16-membered macrolide, was 1.5%. The prevalence of resistance to clindamycin was 1.3%. The majority (98.7%) of the 157 erythromycin-resistant strains presented the M phenotype. When we compared the results obtained in 1998 and 2001, we observed a statistically significant increase in resistance to erythromycin and azithromycin (P = 0.02, chi(2) test), but not to clindamycin or miocamycin (P = 0.47, chi(2) test with Yates' correction). The significant increase in the prevalence of resistance to some macrolides of S. pyogenes in Spain underscores the need for continuous surveillance of antimicrobial resistance in this species.