The sc route was used to study the adjuvant effect of vitamin A palmitate (VA) and the retinoids isotretinoin (Ro 4-3780), etretinate (Ro 10-9359), and motretinide (Ro 11-1430) on cell-mediated immunity to sheep red blood cells (SRBC) in outbred Mai:NIH(S) mice. The immune response was quantified by a sensitive assay procedure in which the antigen is injected intracutaneously into the pinna of the mouse, and the subsequent inflammatory swelling is measured with calipers. A single simultaneous injection of 150 microgram VA enhanced cell-mediated immunity to SRBC as early as 3 days following immunization, and the enhancement persisted for at least 3 weeks. Administered as a single injection 1 day or more before or after SRBC or as an ip injection, VA was not effective. Single injections of 100 microgram isotretinoin and motretinide but not etretinate also enhanced the response. The effective agents possessed adjuvanticity comparable in magnitude to that of Bordetella pertussis vaccine.