Production of neutralizing antibodies was followed in guinea pigs, rabbits, hamsters and mice immunized with crude antigen extracts (AM) from human diploid cells infected with herpes simplex virus type 1. The AM induced relatively high levels of neutralizing antibodies in all four species. The antibodies were predominantly complement-requiring and remained so even after administration of repeated AM doses. With the strains used, the antibody response was predominantly type specific and, surprisingly, the type specificity of sera usually increased after administration of repeated doses of AM. Guinea pigs seemed to be the best responsive animal species. They developed the highest levels of antibodies and complement-nonrequiring antibodies were seen in them earlier than in the other animal species. The dose-response experiments carried out in guinea pigs indicated that after a single dose administration the ratio between complement-requiring and complement-nonrequiring antibodies was dependent on the amount of antigen administered. When AM was given without adjuvant less efficient antibody production wws observed than after the administration of the same amount of antigen with adjuvant.