The interface between insanity, race and culture was a challenging subject for some of the most influential nineteenth-century alienists. Our paper reviews some of the theoretical and clinical investigations of comparative psychiatry of this period. The idea that insanity was supposedly rare among 'primitive' people, e.g., Africans, American Natives and some Eastern populations, was repeatedly defended by prominent alienists. Associated with this notion, many authors believed that insanity tends to become more prevalent as civilization evolves. According to them, civilization had an unfavourable effect on insanity rates because it demanded a much higher degree of organization and mental production. Moreover, a greater degree of mental excitation would explain why insanity occurs more frequently in Europe than in the East, Africa or South America. Eventually, at the end of the nineteenth century, the coalition of cross-cultural and neuropsychiatry produced a notion that the brain of the 'native' is more simple and crude than that of the civilized, and more vulnerable to the evil effects of civilized life. In conclusion, some ethnocentric bias and racial stereotypes still pervasive in contemporary psychiatry are identified and traced back to their historical origins.162155169