1. Natural killer cell activity and monocyte cytotoxicity was evaluated in three subgroups of patients with primary hypogammaglobulinaemia (ten patients with late-onset, eight with X-linked and five with early-onset disease) and in two patients with secondary late-onset hypogammaglobulinaemia against the K-562 erythroleukaemia, the CaCo-2 colon carcinoma and the HGT-1 gastric carcinoma cell lines and compared with the results found in healthy control subjects. 2. The natural killer cell activity, both spontaneous and after stimulation with recombinant gamma-interferon, was found to be decreased in patients with late-onset hypogammaglobulinaemia. The natural killer cell activity in this subgroup was found to be impaired in 60% of the patients (P less than 0.05). Within the other forms of primary hypogammaglobulinaemia a decreased natural killer cell activity was found to be less frequent (33%). 3. The lectin-mediated cytotoxicity by phytohaemagglutinin resulted in a similar maximal cytotoxicity in patients and control subjects. 4. The cytotoxicity of monocytes, spontaneous and after recombinant gamma-interferon stimulation, was found to be normal in all patients with hypogammaglobulinaemia. 5. The impaired natural killer cell activity which was found in patients with late-onset hypogammaglobulinaemia may contribute to the increased susceptibility to infections and to the increased incidence of malignancies in this subgroup of patients with primary hypogammaglobulinaemia.