As part of the ongoing multinational SENTRY antimicrobial resistance surveillance program, a total of 1,047 respiratory tract isolates of Streptococcus pneumoniae, 845 from 27 United States medical centers and 202 from seven Canadian institutions, were collected between February and June 1997 and characterized in a central laboratory. In the United States, the overall percentages of penicillin-intermediate strains and strains with high-level resistance to penicillin were 27.8% and 16.0%, respectively. In Canada, these values were 21.8% and 8.4%, respectively. Among the 31 centers in the United States and Canada that contributed at least 19 isolates, the combined rate of intermediate plus resistant strains varied between 24.0% and 67.8%. The in vitro activity of 19 other antimicrobials was assessed against all study isolates. Overall rates of resistance among selected agents in the United States and Canada, respectively, were as follows: amoxicillin, 18.1% and 10.5%; cefaclor, 38.3% and 26.2%; cefuroxime, 19.5% and 12.9%; cefpodoxime, 18.6% and 11.4%; cefepime, 8.2% and 4.5%; cefotaxime, 4.0% and 3.0%; macrolides (i.e., erythromycin, azithromycin, and clarithromycin), 11.7%-14.3% and 5.0%-7.4%; clindamycin, 3.5% and 3.5%; chloramphenicol, 3.9% and 4.0%; tetracycline, 10.2% and 10.9%; and trimethoprim-sulfamethoxazole, 19.8% and 15.8%.