1. Our aim was to determine the relationship between efferent sympathetic nervous system activity to skeletal muscle (MSNA) and both the dynamics of the stimulus and pain sensation during localized skin cooling in humans. MSNA in the lower leg (peroneal microneurography), heart rate, arterial blood pressure, hand skin and muscle temperatures and perceptions of pain were recorded in ten healthy subjects before, during and after immersion (3 min) of a hand in water of different temperatures ranging from non-noxious to extremely noxious (28, 21, 14, 7 and 0 degrees C). 2. Immersion produced an abrupt, water temperature-dependent fall in hand skin temperature (initial 30 s) followed by a more gradual decline. In contrast, the fall in hand muscle temperature was almost linear during immersion. Throughout immersions at the 28, 21, and 14 degrees C water temperatures and during the initial phase of the 7 degrees C level, sensations ranged from not painful to somewhat painful; however, the latter phase of the 7 degrees C immersion and the entire 0 degrees C level were perceived as intensely painful. 3. During the initial 15-30 s of immersion at the 21-7 degrees C water temperatures, MSNA decreased from control levels in all subjects (47-58% on average, P < 0.05), whereas mean arterial blood pressure did not change. MSNA then returned to and remained at control levels throughout the 28-14 degrees C immersions, although arterial pressure, primarily systolic, rose slightly. 4. After some delay, MSNA increased during immersion at both the 7 degrees C (P < 0.05 at 90 s) and 0 degrees C (P < 0.05 at 60 s) levels in a progressive, water temperature-dependent manner, achieving peak values of approximately 200 and 300% of control, respectively, by 2.0-2.5 min. These elevations in MSNA were associated with parallel increases in arterial pressure. 5. Heart rate rose during the onset of immersion at all water temperatures (P < 0.05), but fell rapidly to control levels after 60-90 s. The increases were small (approximately 5 beats/min) and similar at the 28-7 degrees C levels, but were twice as great at the coldest water temperature.(ABSTRACT TRUNCATED AT 400 WORDS)