BACKGROUND: T cell response to mycobacterial antigens may be directed against those antigens common to all mycobacteria (group i), those restricted to slow (group ii) or fast growers (group iii), or those which are species- or subspecies-specific (group iv). These responses were assessed by skin testing patients infected with the human immunodeficiency virus (HIV) and healthy controls with reagents derived from different strains of mycobacteria. METHODS: Skin test responses to new tuberculins prepared from Mycobacterium tuberculosis, M avium serotypes 4 and 8, and either M intracellulare or M flavescens antigens were evaluated prospectively in 51 HIV infected patients and 67 healthy controls. RESULTS: Assessment of induration at 72 hours showed absence of skin test response to common mycobacterial antigens in all 27 HIV positive patients with CD4 counts of > or = 400/mm3 (range 400-1594, median 540) compared with 27% reactivity in controls; complete anergy was demonstrated in 24 patients with CD4 counts of < 400/mm3. By contrast, no difference in species or subspecies-specific responses was found between healthy controls and HIV positive patients with CD4 counts of > or = 400/mm3. CONCLUSIONS: Subsets of CD4+ T helper cells are instrumental in determining the balance between cell-mediated and humoral immunity. One T helper subset (TH1) produces cytokines that increase cellular immunity and is stimulated by group i common mycobacterial antigens. Lack of this response, but preservation of responses to species-specific antigens while CD4 counts are near normal, may indicate an early failing of TH1 immunity and explain the increased susceptibility of HIV positive patients to mycobacterial infection early on in the evolution of their HIV infection.