Strains of Neisseria meningitidis isolated from patients and asymptomatic individuals who had been in contact with patients were investigated using four typing methods with the aim of identifying any heterogeneity and/or homogeneity among the strains. In 1993, a dramatic change in the incidence and severity of invasive meningococcal disease in the Czech Republic occurred as a consequence of the appearance of a Neisseria meningitidis strain of phenotype C:2a:P1.5,2 and electrophoretic type ET-15, belonging to the ET-37 complex, which had not previously been identified in this country. Presented here are the results of a study of the relationships between 58 Neisseria meningitidis isolates collected between January 1997 and June 1998. Forty-nine isolates originating from patients with invasive meningococcal disease and nine from healthy contacts were analyzed using the following four methods: whole-cell enzyme immunoassay, multilocus enzyme electrophoresis, pulsed-field gel electrophoresis, and randomly amplified polymorphic DNA analysis. A high prevalence of phenotype C:2a:P1.5,2 electrophoretic type ET-15 was confirmed among the patients' strains. Nevertheless, during the study period, they became heterogeneous. Strains isolated from healthy contacts showed greater heterogeneity in serological phenotypes and electrophoretic types from the beginning of the study, and electrophoretic type ET-15 strains were less frequent. Within the electrophoretic type ET-15 clone, strains showing the identical serological phenotype (with the exception of one isolate) were indistinguishable using randomly amplified polymorphic DNA analysis, while pulsed-field gel electrophoresis revealed heterogeneity with 12 pulsed-field gel electrophoretic types identified. The strains from the same cluster displaying the same serological phenotype were indistinguishable with any of the methods used.