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Sixty-six strains of Streptococcus pneumoniae isolated in different parts of the world, 46 resistant and 22 susceptible to penicillin, were subdivided by multilocus enzyme electrophoresis into 28 distinct electrophoretic types (ETs). The ETs to which penicillin-susceptible strains were assigned differed from those containing resistant isolates of the same serotype. Five common clones could be recognized among the penicillin-resistant bacteria by combining the ETs, the antigenic properties of penicillin-binding proteins PBP 1a and 2b, and the tetracycline and chloramphenicol resistance profiles. Two clones were found in Finland and were associated with capsular serotypes 6B and 23F, respectively. Two clones were from Spain (type 6B and 9V, respectively). The fifth clone was isolated in South Africa and in Spain and contained both serotype 23F isolates and one type 19F strain. The other resistant strains were represented by rare isolates distributed among 12 other ETs, confirming that resistance to penicillin has evolved by multiple branches. Because capsular type was mixed in several ETs, the results also demonstrate that it may vary among very closely related pneumococci.