The morbidity from juvenile laryngeal papillomatosis (JLP), a disease process characterized by recurrent growth of multiple epithelial papillomas, has greatly improved with the advent of immunomodulating agents used in combination with the surgical approach of CO2 laser vaporization. In prospectively evaluating the immunologic status of four pediatric patients with this disorder, one patient repeatedly demonstrated IgG2 subclass deficiency. One of two children found to have subnormal functional natural killer (NK) activity received thrice weekly intramuscular administration of 3,000,000 units/m2 body surface area of human leukocyte (alpha) interferon (IFN). Natural killer function normalized, but therapy was discontinued after 4 months; however, no clinical benefits from IFN administration were observed. Further in vitro evaluation of NK function and lymphokine production is needed, in order eventually to offer more effective immunomodulating agents to such patients. A brief review of the literature concerning JLP is also presented.