The efficacy of penicillin G was evaluated in the prevention of infections caused by streptococci in patients receiving remission induction or intensive consolidation treatment for acute myeloid leukaemia. Between 1980 and 1988, 29 episodes of streptococcal septicaemia occurred in 139 treatment events. All patients received as prophylaxis regimen ciprofloxacin (n = 38) or a combination of polymyxin B with nalidixic acid (n = 42) or neomycin (n = 59). Six patients died of streptococcal septicaemia despite adequate antibiotic treatment. The high incidence of streptococcal septicaemia lead to the administration of penicillin G in addition to ciprofloxacin as prophylaxis regimen during the 14 days immediately following cytotoxic chemotherapy. Only two episodes of streptococcal septicaemia were documented after addition of penicillin G to the prophylaxis regimen (n = 76, p < 0.001). Both patients had an uneventful recovery after treatment with vancomycin. Patients receiving penicillin G prophylaxis experienced fever during 17% of the time and received antimicrobial therapy during 20% of the time per treatment event compared with 27% and 32% respectively of this time in patients receiving no streptococcal prophylaxis (p < 0.001). Penicillin G prophylaxis was associated with an increased incidence of fever of unknown origin and more frequent isolation of aerobic gram-negative bacteria in surveillance cultures. Penicillin G in combination with ciprofloxacin proved to be highly successful in preventing infections caused by streptococci and in reducing infection-related mortality and morbidity.