Defects of immunoregulation which occur in haemophilia, reflected by numerical changes in T lymphocyte subsets, have been further investigated in functional studies. Polyclonal T-cell activation by the mitogen phytohaemagglutinin (PHA) and specific stimulation by cytomegalovirus (CMV) or herpes simplex type 2 (HSV-2) in previously sensitized subjects were studied in peripheral blood lymphocyte and in T4-cell-enriched cultures. Compared with 12 controls, the responses of 11 patients (nine with haemophilia A and two with von Willebrand's disease) to PHA were significantly reduced both in unfractionated and in T4-cell-enriched peripheral blood lymphocyte cultures. Reduced responses to PHA were found in HIV (HTLV III)-seronegative as well as -seropositive patients. There were no significant differences between the response of patients' unfractionated and T4-enriched peripheral blood lymphocytes to CMV/HSV-2 recall antigen and the control subjects, although there was evident variation in the magnitude of patients' unfractionated and T4-enriched lymphocyte responses.