Fifty-six patients receiving remission induction treatment for acute leukemia were studied in a randomized trial comparing ciprofloxacin with trimethoprim-sulfamethoxazole plus colistin for prevention of infections. Both groups received amphotericin B for antifungal prophylaxis. Six major infections occurred in 28 patients receiving ciprofloxacin, and 11 major infections occurred in 28 patients receiving trimethoprim-sulfamethoxazole plus colistin. No infections caused by gram-negative bacilli were seen in the ciprofloxacin group (p less than 0.02). Ciprofloxacin prevented colonization with resistant gram-negative bacilli, but 12 resistant colonizing strains were isolated from 10 patients receiving trimethoprim-sulfamethoxazole plus colistin (p less than 0.01). Ciprofloxacin was better tolerated: 23 of 28 patients were highly compliant to the drug, compared with 15 of 28 patients in the trimethoprim-sulfamethoxazole group (p less than 0.05). These results suggest that ciprofloxacin is a promising drug for the prevention of infection in patients with granulocytopenia.