Natural killer activity of peripheral blood mononuclear cells against the human cell line K 562 was evaluated in 11 patients with mycosis fungoides and simultaneously in 10 age- and sex-matched controls. In the patient group, nine had no previous treatment and in two topical therapy had been discontinued more than 3 months before. None had any associated disease or concurrent therapy that could interfere with the immune system. Patients with early disease showed a mean specific lysis and a range of individual data similar to the controls whereas patients with advanced disease had a significant defect of natural killer activity at effector: target ratios of 100 : 1, 50 : 1, and 25 : 1, as shown by the Mann-Whitney test. Preincubation of effector cells with alpha-interferon for 1 h in a single patient with low natural killing capacity led to a clear increase of the specific lysis, suggesting reduced functional activity rather than depletion of effector cells.