Two battery tests were conducted to study the anticryptosporidial prophylactic efficacy of the 2 commercially available antibiotics, enrofloxacin and paromomycin. The efficacy of enrofloxacin was 52% at the recommended level, which could not be increased, using twice the recommended dose. At the recommended levels, paromomycin reduced the oocyst output of birds by 67–82%, showing the highest efficacy of all drugs tested against avian cryptosporidiosis thus far. Moreover, the patent period was shortened by 12–23%. The body weight gain of paromomycin-treated chickens was almost identical with that of uninfected, untreated control birds irrespective of dosage, indicating the lack of toxicity. Although paromomycin is not registered for use in birds, in combination with sanitary procedures and disinfection, it may help in the control of cryptosporidiosis in some bird facilities.