A healthy individual at risk for human immunodeficiency virus type 1 (HIV-1) infection was studied longitudinally for 19 months for evidence of exposure to and infection with HIV. Peripheral blood mononuclear cells (PBMC) were tested at 1, 5, 13, 16, and 19 months for T helper (Th) cell function by in vitro-generated proliferation and interleukin-2 production in response to four synthetic peptides corresponding to env of HIV. PBMC were also tested for proviral DNA using gag primers by the polymerase chain reaction (PCR) at 0, 5, 10, 13, 16, and 19 months. HIV serology by ELISA and p24 antigen and Western blot analyses were done on samples taken at 0, 1, 5, 10, 13, 16, and 19 months. The results indicated that both Th cell tests were positive during months 5-19. In contrast, the PCR and all serologic assays were negative except for month 19, when the assays became positive. These results, based on the longitudinal study of one individual, showed that the Th cell tests can reveal exposure to HIV-1 antigens several months before evidence of viral infection is detected, even by PCR.