Ten micrograms of trehalose-6,6' -dimycolate (cord factor) injected into the footpads of mice increased the antibody response to sheep red blood cells (SRBC) subsequently injected into the same sites. There is a relationship between the antibody response and the cellular reaction induced locally and in the draining lymph nodes by cord factor, as judged by a much weaker response when antigen is injected into the contralateral footpads. The time intervals between injection of cord factor and antigen were from 5 to 20 days. A similar increased antibody response to SRBC was evident after preliminary administration of Freund's complete adjuvant or living BCG bacilli into the footpads. There was no increased antibody response in mice pretreated with living BCG or Freund's adjuvant to SRBC injected into the contralateral footpads. Administration of wax D from human strains Peurois and Test was without any effect. Administration of SRBC emulsified in incomplete Freund's adjuvant containing 5 mug of cord factor induced a very strong antibody response in the mice as compared to that after injection of the same amount of antigen in incomplete Freund's adjuvant containing wax D or mycobacteria. The results are discussed.