Seven consecutive patients who presented with a severe acute mononucleosis-like illness associated with HIV seroconversion were evaluated by T-cell subset enumerations and measurements of lymphocyte transformation responses to mitogens and antigen during both their primary illness and a 1-year follow-up period. We observed a characteristic pattern of response to primary HIV infection; initial lymphopenia was followed by CD8 lymphocytosis and inversion of the CD4:CD8 ratio. During follow-up, the CD8 count gradually returned to normal, whereas the CD4:CD8 ratio remained inverted because of a relatively low number of CD4 lymphocytes. Primary infection was followed by prolonged and severe cellular hyporesponsiveness to both mitogens and antigen. At the last follow-up, responses to pokeweed mitogen were still severely impaired, with a median 19% (range 7-50%) of that observed in healthy controls. We conclude that severe primary HIV infection may be followed by sustained lymphocyte hyporesponsiveness, a sustained low percentage of CD4 lymphocytes and sustained inversion of the CD4:CD8 ratio.