This study determined whether the development of delayed ischemic sequelae due to cocaine use--after the return of arterial blood pressure (BP) and heart rate to near-baseline values--may be attributable to regional vasoconstriction which persists beyond the acute systemic hemodynamic response. Five cocaine-using volunteers received intravenous infusions of saline placebo and cocaine 0.50 mg/kg several days apart in a double-blinded cross-over design. The intensity and duration of the cocaine-induced decrease in peripheral blood flow (as documented by laser Doppler flowmetry of the finger) were compared to the increases in BP (obtained with a Dinamap) and heart rate using paired t-test and repeated-measures analysis of variance. A significant increase in BP and a significant decrease in finger flow were noted by the first time point (5 min). Within 15 min, cocaine induced a 36% +/- 5% increase in BP and a 73% +/- 18% decline in finger flow (P < 0.05 for difference between percent change in BP and percent change in flow). Dinamap(systolic) and Dinamap(diastolic) returned to within 15% of baseline within 30 min, while finger flow remained more than 50% below baseline for the remainder of the 60-min study period (P < 0.05). Changes in heart rate paralleled those in BP. Except for isolated cases of documented coronary vasoconstriction in patients presenting with complications after cocaine use, this study is the first to document the persistence of cocaine-induced vasoconstriction of a sensitive vascular bed beyond the hypertensive response. It thus helps to explain the development of ischemic injury after cocaine use despite a stable rate-pressure product.