Although recent research has focused on "crack" cocaine, the majority of the cocaine users in the United States insufflate ("snort") cocaine rather than smoke it. Furthermore, the intranasal route of administration is often the first way that many cocaine-dependent individuals used cocaine. Numerous studies have reported on the effects of repeated doses of smoked or intravenous cocaine, the relationship between cocaine plasma level and cocaine's effects, and the development of acute tolerance to smoked or intravenous cocaine. Significantly less information is available about similar effects of intranasal cocaine. The purpose of this study was to determine the dose-dependent effects of repeated intranasal cocaine in humans. Ten experienced male cocaine users were admitted to the hospital on two separate occasions for four days each, with a minimal two-week interval between admissions. During each admission, an intranasal cocaine (0.06, 0.34, 0.69, and 1.37 mg/kg) dose-response curve was determined during four laboratory sessions: Two administrations of the same cocaine dose occurred each session at 40-min intervals. Intranasal cocaine produced dose-related increases in ratings of "positive" drug effects, heart rate, and blood pressure. Plasma cocaine levels peaked following the second cocaine insufflation of each session, while metabolite levels increased during each session. Although the plasma cocaine level approximately doubled following the second cocaine administration, the ratings of positive drug effects, heart rate, and blood pressure did not increase after the second cocaine administration. These data demonstrate that, as observed with smoked and intravenous cocaine, acute within-session tolerance develops during repeated intranasal cocaine administration.