Cell-mediated immune response to herpes simplex antigen was assessed by lymphocyte transformation in vitro using cells from 21 volunteers with either frequent or occasional recurrent cold sores. All had significant responses to the viral antigen. Only four of 28 subjects without herpes simplex infections had positive responses. All those with detectable complement-fixing antibody to the virus showed increased lymphocyte stimulation, but three subjects who had only occasional infections had no detectable antibody and yet still showed a significant degree of lymphocyte stimulation. There was no difference between the groups in responses to PHA, PPD, or streptokinase. Eight subjects with recurrent infections were tested with intradermal herpes simplex and control antigens. All showed significant induration in response to the viral antigen at 48 hours. No evidence that there is any defect in this parameter of the cell-mediated immune response in persons with recurrent herpes simplex infections could be shown.