The purpose of this study was to determine the effect of the size of the stimulus area on the muscle sympathetic nerve activity (MSNA), systolic arterial blood pressure (SAP), and heart rate responses to the cold pressor test. To accomplish this, these variables were measured before (control), during, and after 1.5 min of ice water immersion of either one or both hands in nine healthy subjects (aged 19-27 years). The cold stimulus elicited significant increases above control levels in all three variables under both conditions (P less than 0.05). Immersion of both hands produced a much greater increase in total MSNA (+366%) than immersion of a single hand (+187%) (P less than 0.05). However, the magnitudes of the increases in SAP and heart rate during two-hand immersion (29 +/- 6 mmHg and 10 +/- 2 beats min-1) were not significantly different from the responses during the one-hand trials (24 +/- 5 mmHg and 6 +/- 2 beats min-1, P greater than 0.05). There was a strong, direct relationship between total MSNA and SAP responses during one-hand immersion (r = 0.93, P less than 0.001) but not during immersion of both hands (r = 0.66, P = 0.08). These findings indicate that during the cold pressor test the magnitude of the increase in sympathetic discharge to skeletal muscle, but not the systolic blood pressure response, is influenced by the size of the tissue area exposed to the stimulus.