Exposure to human immunodeficiency virus (HIV) does not necessarily induce infection or seroconversion defined by standard criteria based on enzyme-linked immunosorbent assay (ELISA), Western Blot, or polymerase chain reaction (PCR) techniques, but it can induce HIV-specific cell-mediated immune responses. Healthcare workers (HCWs) occupationally exposed to HIV represent a unique population with low-level exposure to HIV for whom time and type of exposure are specifically recorded. Although the frequency of seroconversion in HCWs occupationally exposed to HIV contaminated body fluids is relatively low, a higher proportion of HIV-exposed HCWs seem to exhibit in vitro cellular responses to HIV envelope peptides. Our findings indicate that parenteral exposure to HIV can induce cell-mediated immune responses in the absence of seroconversion. The significance of these responses is not known, but it is possible that the low incidence of HIV infection after exposure might be due, in part, to a protective cellular immune response to low HIV inocula.