Of six evaluated aminoglycosides, paromomycin was the only one that showed activity against Cryptosporidium parvum in immunosuppressed rats. Oral dosages > or = 200 mg/kg/day reduced the severity of ileal infections; however, paromomycin was ineffective against cecal and biliary tract infections at 400 mg/kg/day orally and 50 mg/kg/day intraperitoneally. Oral paromomycin (400 mg/kg/day) was also less effective than azithromycin (400 mg/kg/day) against Cryptosporidium infection involving the ileum, cecum, or biliary tract of immunosuppressed rats. The data suggest that paromomycin may be an effective treatment for acute cryptosporidiosis of the small intestine but is probably ineffective against large intestine or biliary tract infections in the immunosuppressed host.