Myelin-associated glycoprotein (MAG) is susceptible to proteolysis by a calcium-activated neutral protease which is located in myelin. The conversion of MAG (M(r) 100,000) to its soluble derivative dMAG (M(r) 90,000) occurs much more rapidly in myelin from human white matter than in myelin from rat brain, and the rate of formation of dMAG is increased even more in myelin from white matter of patients with multiple sclerosis (MS). The MAG to dMAG conversion was studied in several species, ranging from mice to non-human primates and humans to determine what animal model would be the most appropriate for investigating the MAG to dMAG reaction in demyelinating disorders. Myelin fractions from brains of these species were prepared and incubated at 37 degrees C in 0.2 M NH4HCO3, pH 7.4 for time periods ranging from 5 min to 24 h. Western blot analysis of the samples, taken at the end points of the different incubation periods, showed that the time required for a 50% conversion of MAG to dMAG was 18-24 h in myelin from rodents to bovine. The non-human primate studies revealed a 50% conversion at 2 h for marmoset samples and rhesus monkey samples, 20 min for gorilla samples and 10 min for chimpanzee samples. Human myelin samples needed only 5 min for a 50% conversion of MAG to dMAG. The reason for the significantly faster formation of dMAG in primate myelin is unknown and currently is being investigated.