Although there are many studies of the residential segregation of ethnic groups in cities in various parts of the world, very few address the degree to which segregation levels vary across an urban system, let alone rigorously analyse those variations. Data on segregation across all US Metropolitan Statistical Areas (MSAs) in 1980 and 2000 at the census tract scale have been analysed, using a modified index of isolation, to examine variations in segregation levels, according to their size, the relative size of the various ethnic minorities there, their ethnic diversity, and their location. Strong relationships are identified for all three of the country's major ethnic minority groupsBlacks, Asians and Hispanics. These suggest that Asians and Hispanics are disadvantaged in the labour and housing markets, so that as their number increases so does their level of segregation. Blacks are disadvantaged too: their segregation is compounded by a legacy of decades of discrimination, especially in the older-established parts of the country.