Soluble antigens (Ags) in the extracellular fluids are excluded from the class I major histocompatibility complex (MHC)-restricted pathway of Ag presentation in most cells. However, an exogenous Ag can be internalized, processed, and presented in association with class I MHC molecules on specialized Ag-presenting cells (APCs). These APCs express class II molecules and can simultaneously present exogenous Ags to both class I and class II MHC-restricted T cells. These APCs may be important participants in the regulation of host immune responses. This APC activity may explain several phenomena of cytotoxic T lymphocyte (CTL) priming in vivo and might be exploited for eliciting CTL responses to protein vaccines.