Induction in mice of marked photoallergic contact dermatitis (PCD) to 3,3',4',5-tetrachlorosalicylanilide (TCSA) with UVA (320 to 400 nm) radiation requires pretreatment with cyclophosphamide (CY). Attempts to induce photoallergic contact dermatitis without CY result in only a small degree of sensitivity, accompanied by significant net splenic suppressor cell activity. These suppressor cells are antigen specific, inhibit the induction but not the elicitation of photoallergic contact dermatitis to TCSA, and are T lymphocytes. Exposure of mice to UVB (280 to 320 nm) radiation at a site distant from that of sensitization, before CY administration and sensitization, inhibits the development of photoallergic contact dermatitis. This is analogous to the suppression of allergic contact dermatitis (ACD) observed in mice after exposure to UVB radiation; such suppression is accompanied by the formation of antigen-specific splenic suppressor cells. However, in contrast to the findings with allergic contact dermatitis, splenic suppressor cells are not detected in mice that are treated with UVB radiation before CY administration and sensitization to TCSA. This is presumably because CY prevents their formation. This provides evidence that UVB-irradiated mice have a second form of anergy that is not mediated by suppressor cells.