This article reports on lamp fouling during on-line ultraviolet (UV) sterilization of cheese whey. The extent of fouling as well as the composition of fouling materials was studied after the operation of three tubular UV reactors of different flow thicknesses (18,13, and 6 mm) for 48 h at a 2-h residence time. Lamp fouling, which significantly affected the sterilization efficiency, was realized after an extended period of operation. The extent of lamp fouling increased with a decrease in the thickness of the flowing cheese whey (14.42, 15.31, and 25.25 g for 18-, 13-, and 6-mm thickness, respectively). A strong relationship between the extent of fouling and the steady-state outlet temperature was observed. The fouling material contained 63.51 to 77.19% protein, 12.57 to 16.49% fat, and 6.51 to 9.47% minerals on dry weight bases compared with 1% protein, 0.5% fat, and 0.4% minerals in raw cheese whey. The organic and inorganic material concentrations in the fouling material increased with a decrease in the flow thickness. The fouling mechanism was owing to adsorption and direct ion exchange, which were enhanced by the high temperature and low pH attained in the study. Improved designs of UV reactors in which the contact between the flowing material and the quartz surface should be developed.