Acquired immune deficiency syndrome (AIDS) is a newly described syndrome in which patients are susceptible to certain malignancies and opportunistic infections (OI) usually found only in immunosuppressed individuals. Patients with AIDS have been found to have deficiencies of virtually all of their host defense systems. In this report, the natural resistance systems have been discussed. Although a deficiency of NK-cell function has been found in many patients with AIDS, this deficiency failed to distinguish patients susceptible to OI or malignancy from male homosexual controls. A deficiency of interferon-alpha generation by mononuclear cells upon exposure to HSV-1 infected fibroblasts was the best correlate with susceptibility to OI in AIDS patients. This deficiency failed to correlate with serum levels of acid-labile interferon-alpha in these patients. Although the interferon generating deficiency may be caused by the infections in these patients, it is more likely that the deficiency lays the groundwork for the establishment of the opportunistic infections.