Thirty male calves were used in a 2 X 3 factorial arrangement of treatments to determine the effects of dietary nickel and protein on performance, urease activity and tissue concentrations of nickel, iron, zinc, copper and manganese. Protein levels evaluated were 10.0, 12.25 and 14.5%, and nickel was supplemented at a level of 0 or 5 mg/kg of diet. Nickel did not affect growth during the 140-d study but tended to increase efficiency of gain in calves fed 14.5% protein. Rumen fluid urease activity was increased by nickel only in animals receiving the low protein diet. Urease activity in rumen fluid was higher in calves fed 10.0% than in animals fed 12.25% or 14.5% protein. Neither nickel nor protein affected urease activity in rumen epithelium. Increasing dietary protein resulted in increased urease in cecal digesta. Lung, liver, kidney and serum nickel concentrations were increased by supplemental nickel. A nickel X protein interaction was noted for kidney nickel. Nickel supplementation increased kidney nickel to a greater degree in calves fed 10.0% protein than in calves fed higher protein levels. Nickel supplementation reduced iron concentrations in lung, liver and muscle and manganese concentrations in muscle. Increased dietary protein decreased iron in liver and spleen but increased manganese concentrations in heart. These findings indicate that dietary protein influences responses of ruminants to nickel supplementation and relatively small increases in dietary nickel and protein can influence metabolism of other trace elements.