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Cheese processing waste is a complex of miscellaneous liquid wastes from a cheese plant not including standard whey, which is often dried and used for food. During treatment of cheese processing waste (soluble COD > 80,000) using an upflow anaerobic sludge blanket (UASB) reactor in our lab, we found methane production decreased with time. The concentration (mg/l) of Na+ and K+ in the failing UASB was about 5,000 and 1,000, respectively because pH was controlled by adding sodium or potassium hydroxide buffer. We presumed methane decreased because of cheese processing waste toxicity or cation inhibition. This study was undertaken to learn more about the causes of poor performance in the UASB. The anaerobic toxicity assay (ATA) and cation inhibition (CI) assay with two different starters were performed on various dilutions of cheese processing waste and cheese processing waste spiked with cations. Through 62 and 33 days runs for the ATA and CI studies, respectively, the following results were found: (1) Cheese processing waste was not found to be toxic to both starters. (2) Sodium and potassium did not significantly inhibit methane production when municipal waste sludge was used as a starter, but it did significantly inhibit methane production when pig waste sludge was used. In this case, the inhibition concentration of sodium and potassium was 4,887 mg/l and 8,301 mg/l, respectively.