A review of the epidemiology of invasive pneumococcal disease in Scotland was carried out using data from laboratory-based systems during the period 1988–99. This comprised 5456 (90·8%) isolates of Streptococcus pneumoniae from blood, 467 (7·8%) from cerebrospinal fluid (CSF) and 84 (1·4%) from other sterile sites. The mean annual incidence of invasive disease was 9·8/105 population (9·0/105 for bacteraemia and 0·8/105 for meningitis). Invasive disease was highest in children <2 years of age and in the elderly [ges ]65 years (44·9/105 and 28·4/105 population in these age groups respectively). The highest incidence of pneumococcal meningitis, 11·8/105 persons occurred in children <2 years of age. Males had a higher incidence of pneumococcal bacteraemia and meningitis than females (male[ratio ]female = 1·2[ratio ]1 for bacteraemia (RR = 1·17, 95% CI 1·11, 1·24) and 1·5[ratio ]1 for meningitis (RR = 1·41, 95% CI 1·18, 1·70)). Pneumococcal disease was highest in winter periods and coincided with influenza activity. The proportion of penicillin and erythromycin non-susceptible isolates increased from 4·2% in 1992 to 12·6% in 1999 and from 5·6% in 1994 to 16·3% in 1999 respectively. Our data confirm the substantial and increasing disease burden from pneumococcal disease and rise in prevalence of antibiotic non-susceptibility among pneumococci in Scotland. Continued surveillance of groups at increased risk for pneumococcal disease and the antibiotic susceptibility and serotype distribution of isolates are important to develop appropriate policies for the prevention of pneumococcal disease in Scotland.