The effects of the adjuvant dimethyl dioctadecyl ammonium bromide (DDA) on the immune responses to encephalomyocarditis (EMC) virus were studied in mice. The humoral response, as measured by appearance of neutralizing antibodies, was slightly enhanced in mice immunized by the intraperitoneal route. Intracutaneously, DDA almost did not affect the humoral response but resulted in distinct enhancement of delayed type hypersensitivity (DH), as measured by the footpad swelling test. DH to EMC virus was found to be antigen-specific and could be passively transferred to normal mice with peritoneal exudate cells from immunized mice. Dose-response curves for DH and humoral antibody responses to EMC virus were not concordant. Low doses induced DH on day 6 without measurable circulating antibodies; high doses gave good antibody responses but suboptimal DH reactions. Immunization conferred a state of resistance to infection with virulent EMC virus. Protection seemed more related to DH than to the prevalence of specific antibodies at the time of infection.