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This laboratory recently reported that the blood pressure and muscle sympathetic nerve activity (MSNA) responses to cold pressor testing are greater in normotensive blacks than in age- and weight-matched normotensive whites. The present study was designed to determine the relationship between race, family history of hypertension, and sympathetic response to cold pressor testing. The study used microneurography to measure MSNA responses to cold pressor testing in normotensive blacks with (n = 8) and without (n = 8) and normotensive white subjects with (n = 8) and without (n = 10) a positive family history of hypertension. Resting blood pressure was lower in black subjects without a positive family history of hypertension but otherwise resting blood pressure, heart rate, and MSNA were similar in the four groups. Black subjects with a family history of hypertension manifested a greater increase in blood pressure and MSNA than both white groups. Blood pressure and sympathetic responses of black subjects with a negative family history of hypertension tended to be intermediate and were not statistically different from the other three groups. These results indicate that the greater sympathetic response to cold stress observed in normotensive African-Americans is true only of black subjects with a positive family history of hypertension.