A healthy immunocompetent 26-year-old man developed prolonged symptomatic cryptosporidiosis. He only achieved clinical improvement after treatment with spiramycin. Other family members suffered from chronic undiagnosed diarrhea, and resolution occurred only after a trial of spiramycin. Thus, Cryptosporidium had provoked a prolonged symptomatic infection in a normal host; spiramycin therapy was required for parasite eradication and clinical cure, and a therapeutic trial with spiramycin was beneficial for family members with chronic undiagnosed diarrhea. Many infections with Cryptosporidium have serious morbidity, and thus, spiramycin may be more generally indicated in the treatment of this infection.