Topical application of trifluoroperazine (TFP), a calmodulin inhibitor, on the skin of CBA mice previously immunized with 2-phenyl-4-ethoximethylene-oxazolone (oxazolone) blocks the expression phase of contact sensitivity. More detailed analysis of the TFP-mediated inhibition of contact sensitivity shows that TFP significantly suppresses the passive transfer of contact sensitivity when added in vitro to oxazolone-immune cells at a molar concentration of 10(-4) -10(-5). Furthermore, the DNA synthesis of draining lymph node cells from immune mice challenged with oxazolone was suppressed when cultured in the presence of TFP. The exposure of spleen and lymph node cells from immune animals to recombinant IL-2 fails to modify the TFP-mediated inhibition of passive transfer and cell proliferation. The TFP topical application opens the possibility to use this compound in the treatment of delayed hypersensitivity-caused skin disorders.