A patient with varicella-zoster disease was found to have antibodies to human interferon. These antibodies included all IgG subclasses, showed a high combined affinity (average dissociation constant, 10(-11)M), and were present in serum at a concentration of 10(-9)M. The antibodies neutralized the activity of a series of human alpha-interferons prepared from recombinant DNA as well as that of naturally occurring mixtures of alpha-type interferon prepared by viral stimulation of human cells. Examination of the patient's lymphoid cells revealed normal production of interferon and normal expression of interferon receptors. Interferon from the patient's cells was neutralized by her serum. The neutralizing capacity of this serum was analyzed with regard to levels of interferon previously detected in patients with varicella-zoster infections.