Renal function was investigated in eight normal subjects before and during infusion of dopamine (3 micrograms.kg-1 x min-1) at sea level (SL) and at high altitude (HA, 4,350 m). Lithium clearance (CLi) was used as an index of proximal tubular outflow. HA significantly increased arterial pressure, heart rate, and plasma norepinephrine. Effective renal plasma flow (ERPF) decreased at HA by 10% (P < 0.05), but glomerular filtration rate (GFR), CLi, sodium clearance (CNa), and urine flow remained unchanged compared with SL. Dopamine at SL and HA increased ERPF by 47% (P < 0.001) and 30% (P < 0.01), respectively, but the increase at HA was smaller than that at SL (P < 0.05). Dopamine increased GFR only at SL. CLi and CNa increased by 29% (P < 0.001) and 108% (P < 0.001) at SL and by 23% (P < 0.01) and 108% (P < 0.001) at HA. Whereas dopamine at SL increased urine flow by 46% (P < 0.01), this response was abolished at HA, and free water clearance decreased (P < 0.05). The decreased ERPF at HA suggests a constriction of the renal arterioles secondary to increased adrenergic nervous activity. Although the effect of dopamine on ERPF was attenuated in hypoxia, dopamine-induced increases in CLi and CNa remained unaltered, suggesting that natriuresis in both environments was secondary to an increased outflow from the proximal tubules. The absence of a diuretic response to dopamine at HA seemed to be caused by an effect on distal tubular function.