Orthostatic tolerance is reduced in the heat stressed human. This study tested the following hypotheses: 1) whole-body heat stress reduces baseline cerebral blood velocity (CBV) and increases cerebral vascular resistance (CVR); and 2) reductions in CBV and increases in CVR in response to an orthostatic challenge will be greater while subjects are heat stressed. Fifteen subjects were instrumented for measurements of CBV (transcranial ultrasonography), mean arterial blood pressure (MAP), heart rate, and internal temperature. Whole-body heating increased both internal temperature (36.4±0.1 to 37.3±0.1° C) and heart rate (59±3 to 90±3 beats/min); P<0.001. Whole-body heating also reduced CBV (62±3 to 53±2 cm/sec) primarily via an elevation in CVR (1.35±0.06 to 1.63±0.07 units); P<0.001. A subset of subjects (N=8) were exposed to lower-body negative pressure (LBNP 10, 20, 30, 40 mmHg) in both normothermic and heat stressed conditions. During normothermia, LBNP of 30 mmHg (highest level of LBNP achieved by the majority of subjects in both thermal conditions) did not significantly alter CBV, CVR, or MAP. During whole-body heating, this LBNP decreased MAP (81±2 to 75±3 mmHg), decreased CBV (50±4 to 39±1 cm/sec), and increased CVR (1.67±0.17 to 1.92±0.12 units); P<0.05. These data indicate that heat stress decreases CBV, and the reduction in CBV for a given orthostatic challenge is greater during heat stress. These outcomes reduce the reserve to buffer further decreases in cerebral perfusion prior to presyncope. Increases in CVR during whole-body heating, coupled with even greater increases in CVR during orthostasis and heat stress, likely contribute to orthostatic intolerance.