The in vitro activity of ranalexin alone and in combination with other cationic peptides, macrolides, rifampin, and rifabutin was investigated against a clinical isolate of Cryptosporidium parvum. Susceptibility tests were performed by inoculation of the isolate onto cell monolayers and determining the parasite count after 48 h of incubation at 37 degrees C. Antibiotic-free cultures were used as controls in the study. Ranalexin showed low anticryptosporidial activity: it suppressed the growth of parasites by > or = 40% at 50 microM. Ranalexin showed enhanced activity when it was combined with noninhibitory concentrations of other compounds: a 74.4-94.1% reduction in the number of parasites was observed when ranalexin 50 microM was combined with magainin II 50 microM, indolicidin 50 microM, clarithromycin 8 mg/l, azithromycin 8 mg/l, rifampin 8 mg/l, and rifabutin 8 mg/l. The results suggest that ranalexin may be effective in inhibiting Cryptosporidium parvum growth in vitro upon combination with other peptides and hydrophobic antibiotics.