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Streptococcus pneumoniae is a serious pathogen, responsible for a large proportion of cases of pneumonia, bacteraemia and meningitis. Restriction endonuclease analysis (REA) using Taq I and Hae III was evaluated to analyse the genetic relationships among 51 isolates of S. pneumoniae in four different serotypes. This method was used together with pulsed-field gel electrophoresis (PFGE) in the analysis of clinical isolates of bacteraemic S. pneumoniae in the Grampian region of Scotland during a two year period from 1993-5. A total of 104 isolates were collected, of which 93 were analysed by REA and 94 by PFGE. Sensitivities to eight commonly used antibiotics were determined for 99 isolates, and serotyping was performed by the relevant reference laboratory. Records were available for 92 patients and details of past medical history, primary site of infection and outcome were abstracted. Of the clinical isolates analysed, 1% were fully resistant to penicillin and 12% were resistant to erythromycin. The three most common serotypes were 14(23.5%), 4 (12.2%) and 23F (9.2%). The current vaccine, Pneumovax II, was calculated to provide 99.8% cover for the serotypes isolated. The overall incidence of bacteraemic infection was 10.3 per 100,000 population per year, and the mortality was 21.2%. Both the incidence and mortality increased exponentially with respect to age. In both serotype and clinically based studies, when analysed by REA and PFGE, isolates were primarily grouped into closely associated clusters of single serotypes. Some serotypes, such as 3, 6B and 14, were divided into genetically distinct subgroups. The genetics structure of the population was defined as being primarily clonal with evidence of a serotype change in one instance. An erythromycin resistant serotype 14 clone was described, and later discovered to be of the M phenotype. This clone was significantly associated with bacteraemic disease in the under 5 age group, and was demonstrated to be the current major cause of erythromycin resistance in the U.K.