To test the hypothesis that phenylephrine-induced elevations in blood pressure are attenuated in heat stressed humans, blood pressure was elevated via steady-state infusion of three doses of phenylephrine HCl in 10 healthy subjects in both normothermic and heat stress conditions. Whole body heating significantly increased sublingual temperature by ~0.5°C, muscle sympathetic nerve activity (MSNA), heart rate, cardiac output, and decreased total peripheral vascular resistance (TPR; all P<0.005), but did not change mean arterial blood pressure (MAP; _p>0.05). At the highest dose of phenylephrine, the increase in MAP and TPR from pre-drug baselines were significantly attenuated during the heat stress (MAP: 8.4± 1.2 mmHg; TPR: 0.96± 0.85 PRU) when compared to normothermia (MAP: 15.4 ± 1.4 mmHg, TPR: 7.13 ± 1.18 PRU; all P<0.001). The sensitivity of baroreflex control of MSNA and heart rate, expressed as the slope of the relationship between MSNA and diastolic blood pressure as well as the slope of the relationship between heart rate and systolic blood pressure, respectively, were similar between thermal conditions (each P>0.05). These data suggest that phenylephrine-induced elevations in MAP are attenuated in heat stressed humans without affecting baroreflex control of MSNA or heart rate.