A single dose of 200 mg/day rufloxacin was investigated for preventing infection and for its impact on the commensal flora in a pilot study of 62 patients undergoing cytotoxic treatment for cancer. No infection caused by Gram-negative bacilli occurred among 54 assessable patients but prophylaxis was replaced by empirical treatment for fever in 19 cases and because of an adverse event, in a further three cases. The remaining 32 patients completed prophylaxis. The number of oral Branhamella spp., faecal Enterobacteriaceae and Bacteriodes spp. were significantly reduced whereas there was little effect of rufloxacin on the numbers of the other oral and faecal microflora. However, resistance to rufloxacin increased among both oral viridans streptococci, coagulase negative staphylococci and the faecal enterococci. These preliminary data suggest that selective oral antimicrobial prophylaxis for patients with cancer might be achieved with once-daily rufloxacin.