Dose responses for ultraviolet B light (UVB)-induced suppression of contact sensitivity were studied in mice, with and without cyclophosphamide (Cy) pretreatment, to investigate the role of Cy-sensitive suppression. Mice were irradiated on the back, sensitized on the abdomen, and challenged on the ears. Half of the mice were injected intraperitoneally with 200 mg/kg of Cy 3 days before being sensitized. Ultraviolet B light radiation reduced the ear swelling reactions in a linear relation to the log10 of the dose. Fifty percent suppression was shown by the computer-generated regression line at approximately 4.8 kJ/m2 of UVB radiation, with complete suppression at approximately 65 kJ/m2. In mice pretreated with Cy, ear swelling was increased, showing inhibition of a Cy-sensitive suppressive component of the contact sensitivity reaction. This Cy-sensitive component also was seen in mice treated with UVB, but with higher doses of UVB, there still was a UVB-dose-dependent decline in ear swelling in Cy pretreated mice, and there was complete suppression of reactions with the highest doses of UVB in the Cy-treated mice. Therefore, there is a second mechanism, not sensitive to Cy, that causes UVB-induced immune suppression.