We contend that perceived discrimination has an independent effect on depression outcomes among adults of Mexican origin. Using a sample of 3,012 Mexican-origin respondents in Fresno, California in 1995/96 (ages 18-59) we investigate the direct and moderating connections between perceived discrimination, acculturative stress, and mental health (CES-D). We also investigate the social patterning of perceived discrimination. While more highly acculturated immigrant respondents were more likely to experience discrimination than their less acculturated counterparts, more highly acculturated U.S. born respondents were less likely to experience discrimination. Discrimination was directly related to depression, but this effect was moderated through nativity/country of residence, English-language acculturation, sex, and country of education variables. Moderate levels of legal status acculturative stress were especially depressive for native-born U.S. residents.