A major protein previously recognized as being primarily associated with the cell walls of Mycobacterium leprae, major wall protein (MWP), is now identified as histoprotein H2b based on N-terminal amino-acid sequencing, electrophoretic comparisons, and several other properties. An avid association between several host/armadillo-derived histones and M. leprae was demonstrated. Since such armadillo-derived M. leprae are the basis of several ongoing vaccine trials, a simple procedure that permits the prompt solubilization and quantification of histones in M. leprae preparations is described. The quantity of histones associated with M. leprae is significant, ranging from 0.6 to 4.8 micrograms of histoprotein H2b per mg of bacteria.