AbstractThirty‐six young adult male and female Syrian hamsters were divided into four groups. Group 1 (N = 6) was treated with mineral oil. Group 2 (N = 12) was treated with 7,12‐dimethylbenz[a]anthracene (DMBA), Group 3 (N = 12) was treated with DMBA and 13‐cis‐retinoic acid (RA), and Group 4 (N = 6) was treated with RA only. The hamsters were treated three times a week for six weeks. When the DMBA‐treated animals were also treated with RA, tumor formation was inhibited. In the DMBA‐treated animals that did not have RA, there was a significant reduction in the number of Langerhans cells (LCs) located interfocally and in foci compared with controls (p≤0.001). The systemic administration of 10 mg of RA significantly increased the number of ATPase‐positive LCs in the focal aggregates (p≤0.001). Interfocally, the number of ATPase‐positive LCs was statistically elevated in pouches from RA‐and DMBA‐treated animals (Group 2 vs. Group 3, p≤0.01). Following the administration of RA (Group 4), there was a statistically significant increase of LCs interfocally compared with Groups 2 or 3 (p≤0.001). RA administered alone resulted in a small increase in foci compared with Group 3 but in a significant decrease compared with the control group (p≤0.001). Systemic RA appears to not only affect the number of ATPase‐positive LCs but also to alter the distribution of these cells in DMBA‐treated pouches. The change in the number and relationship between LCs may effect the cell's ability to preserve local immunity.