Eighty-nine penicillin- and ciprofloxacin-resistant Streptococcus pneumoniae isolates were evaluated by serotyping and pulsed-field gel electrophoresis. Although penicillin-resistant isolates demonstrated considerable homogeneity, resistance to ciprofloxacin did not correlate with a reduction in genotypic variability. These results suggest that, unlike that of penicillin resistance, the spread of S. pneumoniae ciprofloxacin resistance in Canada is currently not attributable to clonal dissemination.