Between April 1982 and June 1983, cryptosporidiosis was diagnosed in six homosexual men. Four patients with the acquired immunodeficiency syndrome had lymphopenia, cutaneous anergy, and profoundly impaired cellular immunity; their cryptosporidiosis was severe, unremitting, and refractory to all therapy. Two patients without other opportunistic infections or Kaposi's sarcoma had moderately impaired cellular immunity but not lymphopenia or anergy; their enteric illness was self-limited. Cryptosporidium recently had been recognized as a human pathogen that is transmitted through fecal-oral contamination. The severity of human cryptosporidiosis appears to be determined primarily by immunocompetence of the patient. These six homosexual men, with different degrees of immunologic impairment, had two clinically divergent forms of cryptosporidiosis. Their cases raise questions about human transmission of Cryptosporidium and the prognostic significance of this disease in patients who are at high risk for developing the acquired immunodeficiency syndrome.