To determine the distribution of beta-2 microglobulin (B2m) alleles in wild mice we have typed mice derived from natural populations in Europe, North Africa, South America, and East Asia. Mus musculus domesticus mice from Germany, France, Italy, and Peru were all B2ma as were most from the United Kingdom. M.m. musculus mice from Denmark and Czechoslovakia, several stocks of M.m. molossinus from Japan, and M.m. castaneus from China, Thailand, and the Philippines were of B2mb type. This is consistent with the notion that C57BL/6 may have obtained some of its genes, including B2m, from Eastern mice. A BglI restriction site characteristic of B2mb was also found in mice from Czechoslovakia and Japan, confirming that B2mb is a naturally occurring allele of B2m. A new type of beta 2m (beta 2mwl) was found in four stocks of M. spretus from Portugal, Spain, and Morocco. This molecule differs in apparent size and charge from the a and b types. Beta 2mw2 was found together with beta 2ma in one stock of M.m. domesticus (brevirostris) from Morocco. Beta 2mw3 and beta 2mw4 were found in a few M.m. bactrianus from Pakistan. In all cases tested, these new beta 2m molecules associate with class I histocompatibility antigens.