Ice nucleating particles (INPs) are rare among atmospheric aerosols. However, through their ability to induce freezing of cloud droplets in cold clouds, they affect cloud lifetime, cloud albedo, and the efficiency and distribution of precipitation. While terrestrial sources of INPs are the focus of much research, the potential of rivers and lakes to be significant INP reservoirs has been neglected. In the first survey of a major river system, surface waters from the Mississippi, Missouri, Platte, and Sweetwater Rivers, all draining east and south from the Great Divide in the United States of America (USA), were tested for their INP concentrations. The survey comprised 49 samples, taken approximately every 150-250 km along 90% of the Mississippi (from Natchez, MS to the source at Bemidji, MN), the full length of the Missouri, 90% of the North Platte, and all of the Sweetwater. Samples were analysed using the immersion freezing method. The highest freezing temperature varied between −4 and −6 • C, and the concentration of INPs active at −10 • C or warmer ranged from 87 to 47,000 mL −1 . The average INP concentration at −10 • C was 4950 mL −1 , almost four orders of magnitude greater than the numbers of INPs typically found active at this temperature in seawater. The majority of INPs (69 to >99%) were heat labile (deactivated by heating to 95 • C) and therefore likely to be biological. Although the surface area of rivers is limited, their significant concentrations of INPs suggest that freshwater emissions should be investigated for their potential impact on regional cloud processes.