Capsid, envelope, and nonvirion-associated soluble components of type 1 and type 2 herpes simplex virus (HSV) were obtained from infected monolayer cell cultures and used as complement fixation (CF) antigens. Capsids were prepared by treatment of cells with the nonionic detergent Nonidet-P40, envelope material by treatment of virions with ether and high pH, and soluble components were obtained from culture fluids of untreated cells. Serological studies with experimental anti-herpesvirus sera indicate that these serotypes share cross-reacting envelope, capsid, and soluble antigens with each other and with herpesvirus B but not with varicella virus. In addition, animals immunized with crude HSV preparations contain high levels of CF antibody (1:32 to 1:64) to soluble antigens, whereas sera from humans who have experienced natural infection contain low levels of antibody (≤1:8) to this antigen. Further testing with reference, capsid, and envelope antigens indicates that antibody levels to reference and capsid antigens are about the same in sera from healthy humans, whereas antibody to the envelope is decidedly lower in these sera. Herpes convalescent-phase sera contain higher levels of antibody to reference and envelope antigens than to capsid antigen.