The prevalence of isolates of Streptococcus pneumoniae (pneumococcus) that are resistant to antimicrobial agents is increasing globally. We studied the connection between antimicrobial resistance of pneumococci and regional use of antimicrobial agents in Finland. In 1997, a total of 6106 pneumococcal isolates were identified in clinical microbiology laboratories in Finland. Most of the pneumococci were isolated from respiratory tract samples, 8% were from blood culture samples, and 0.5% were from cerebrospinal fluid samples. The regional levels of resistance for pneumococci in 1997 were compared with the regional rates of use of antimicrobial agents from 1995 through 1996. We found that resistance to macrolides correlated highly significantly with macrolide use (P=.006). A significant correlation was also found between resistance to trimethoprim-sulfamethoxazole and trimethoprim-sulfamethoxazole use (P=.043). We did not find a correlation between penicillin resistance and the use of any antimicrobial agent. The positive correlation between macrolide-resistant pneumococci and the use of macrolides is worrying, because macrolides are used worldwide in the treatment of patients with respiratory tract infections, which are often caused by pneumococci.