The incidence of Clostridium difficile-associated diarrhoea (CDAD) was investigated retrospectively at a 690-bed teaching hospital for the period 1983–92. Our aims were to determine: (i) the distribution by age and sex of patients with CDAD, (ii) the possibility of a seasonal trend and, (iii) the influence of infection control procedures, contamination of the hospital environment and the use of third-generation cephalosporins. The laboratory diagnosis of CDAD was based on demonstration of the organism by stool culture and/or detection of specific cytotoxin in stool filtrates. C. difficile was detected in 917 patients who were being investigated for diarrhoeal illness. Yearly isolations varied from a low of 49 in 1983 to a high of 120 in 1990 (Chi square for linear trend 128·8; P < 0·005). Most patients were elderly, with 63% aged 60 years or more; the majority (59%) were female. The relationship between culture of C. difficile and detection of cytotoxin in faecal extracts was also examined. Sixty percent of a sample of 132 isolates from patients in whom faecal cytotoxin was not detected produced cytotoxin in vitro, suggesting that culture is a more sensitive indicator of infection with C. difficile than cytotoxin detection. When the total number of faecal specimens received in the laboratory was used as a denominator there was an increase in the number of incident cases of CDAD between 1983 and 1990, apart from 1986. When occupied bed days was used as the denominator a similar trend was observed with a peak in 1990. These increases correlated with an increase in the use of third-generation cephalosporins at SCGH between 1983 and 1989 (Pearson's correlation coefficient, 0·90). The introduction of Body Substance Isolation in 1989, in conjunction with other infection control procedures, appears to have halted the rise, despite a continuing use of broad-spectrum cephalosporins. In order to reduce the number of cases of CDAD, either a reduction in levels of environmental contamination or a reduction in the use of third-generation cephalosporins is required. If this can be achieved the economic consequences, in terms of an opportunity cost, will be considerable.