Background: Sarcoidosis is known to be associated with defects in cellular immunity, especially in reference to T helper lymphocytes. Anergy to a tuberculin skin test is most characteristic of this disease. Objectives: To further the data on impaired immunity, we studied the antibody response to hepatitis B vaccination in patients with sarcoidosis, Methods: Serologic markers of hepatitis B virus (HBV) (HBsAg, anti-HBs, anti-HBc) were studied in 40 patients with sarcoidosis (32 female, 8 male; mean age: 45 +/- 11 years, range: 25-66 years) with a mean duration of disease of 6 years, While a II the markers were negative in 22 patients (55%), 2 had isolated anti-HBc positivity and 16 had both anti-HBc and anti-HBs antibodies. Thirty-five age- and sex-matched healthy subjects were studied as controls, Recombinant HBV vaccines (Genhevac B Pasteur, 20 mug) were administered (at 0, 1, and 6 months) to 16 of the seronegative cases and the controls and antibody titres were measured 1 month after the last dose. The tuberculin skin test was negative in all cases. Results: While none of the vaccinees in the diseased group responded, the control group yielded an antibody response rate of 85.7% (30/35), with a mean titre of 257.9 mlU/ml. Conclusions: Patients with sarcoidosis were invariably unresponsive to standard vaccination, while some of the diseased subjects had already mounted a natural antibody response, either before or after the development of the original disease. Cellular immunodeficiency in sarcoidosis could be a suitable model for studying immunological interactions between HBV and the host. Copyright (C) 2000 S. Karger AG, Basel.