Epidermal cells (EC) enriched for Langerhans cell (LC) content can present tumor-associated antigens (TAA) for in vivo anti-tumor immunity provided they have been activated by exposure to GM-CSF. In order to establish whether TAA-pulsed EC can be used to favorably modify the growth of already existing tumors, the following experiments were done utilizing the S1509a spindle cell tumor (H-2 a ). EC were prepared from CAF 1 (H-2 a ) mice and Thy-1-bearing cells deleted by antibody and complement mediated lysis. They were then cultured for 16 hr in complete medium containing 50 U/ml of GM-CSF followed by exposure to a soluble extract of S1509a cells as a source of TAA for 2 hr. Twenty thousand TAA-pulsed EC were then injected subcutaneously at the site of inoculation of 2 10 6 living S1509a cells in each of 5 mice per group. This immunization was repeated 4 times at 2 day intervals. The immunization protocol was performed at the following time points: first immunization 4 days after tumor inoculation, 2 days after tumor inoculation, at the time of tumor inoculation, 2 days prior to tumor inoculation, 4 days prior to tumor inoculation or 6 days prior to tumor inoculation. The immunization protocol had no effect on tumor growth at any time point except when immunizations were started 4 or 6 days prior to tumor inoculation (in the 4 day experiment mean tumor volume for the non-immunized control group at day 12 was 609.8 +/- 201.0 (SEM) mm 3 versus 111.3 +/-43.2 mm 3 for the immunized animals, p=0.004). These data indicate that the S1509a tumor rapidly induces a state of tolerance after inoculation into mice that is difficult to break by the use of TAA-pulsed epidermal antigen presenting cells.