The tyrosinase activity of Himalayan mouse skin homogenates was measured over a range of temperatures using two sensitive radiometric assay--namely, (1) the measurement of 14C-tyrosine incorporation into melanin, and (2) the measurement of 3HOH released as a by-product of 3H-tyrosine hydroxylation. Results show that Himalayan tyrosinase is maximally active at temperatures well below normal body temperature (15 degree C to 25 degree C). These results are in support of Danneel's visual observations ('41) that "ferment" activity of Himalayan rabbit skin is absent at temperatures above 25 degree C. Further results suggest the presence of a tyrosinase inhibitor in Himalayan mouse skin. First, removal of a low molecular weight fraction from Himalayan skin homogenates resulted in an increase in tyrosinase activity. Second, recombination of the low molecular weight fraction to the homogenate from which it was originally separated resulted in a decrease in tyrosinase activity when assayed at 37 degree C, but no decrease when assayed at 25 degree C. It is proposed that at the normal body temperature of 37 degree C, tyrosinase from Himalayan skin is strongly bound to an inhibitor. At lower body temperatures, the affinity of the enzyme for the inhibitor decreases, thus allowing the synthesis of melanin to increase. This change in affinity of the enzyme for the inhibitor could be regulated by temperature-induced conformational changes in either the enzyme or the inhibitor or both.