The U.S. Geological Survey-in cooperation with the U.S. Army Corps of Engineers, The Nature Conservancy, the Real Edwards Conservation and Reclamation District, and the Texas Parks and Wildlife Department-investigated streamflow gain and loss and water quality in the upper Nueces River Basin, south-central Texas, specifically in the watersheds of the West Nueces, Nueces, Dry Frio, Frio, and Sabinal Rivers upstream from the Edwards aquifer outcrop. Streamflow in these rivers is sustained by groundwater contributions (for example, from springs) and storm runoff from rainfall events. To date (2012), there are few data available that describe streamflow and water-quality conditions of the rivers within the upper Nueces River Basin. This report describes streamflow gain-loss characteristics from three reconnaissance-level synoptic measurement surveys (hereinafter referred to as \“surveys\”) during 2008-10 in the upper Nueces River Basin. To help characterize the hydrology, groundwater-level measurements were made, and water-quality samples were collected from both surface-water and groundwater sites in the study area from two surveys during 2009-10. The hydrologic (streamflow, springflow, and groundwater) measurements were made during three reconnaissance-level synoptic measurement surveys occurring in July 21-23, 2008; August 8-18, 2009; and March 22-24, 2010. These survey periods were selected to represent different hydrologic conditions. Streamflow gains and losses were based on streamflow and springflow measurements made at 74 sites in the study area, although not all sites were measured during each survey. Possible water chemistry relations among sample types (streamflow, springflow, or groundwater), between surveys, and among watersheds were examined using water-quality samples collected from as many as 20 sites in the study area. During the three surveys, reaches of gaining, losing, or no verifiable change in streamflow were observed in the watersheds in the study area. Reaches of generally consistent gaining or losing streamflow were identified in the Nueces, Frio, and Sabinal River watersheds. The water-quality data indicate that the streamflow, springflow, and groundwater have similar major ion chemical characteristics and generally can be categorized as a calcium-carbonate water type. Those data also indicate that the major ion chemistry was similar during the 2009 and 2010 surveys. Graphical comparisons among ratios of major ions, trace elements, and isotopes (for example, magnesium/calcium ratios to strontium isotopic ratios) indicate that samples collected from each watershed generally clustered together. Determining the source areas and other possible contributors on the basis of these data is not possible because of the small sample size of the water-quality dataset (both in number of samples and spatial distribution of samples). The different relations among the water-quality data indicate that the surface water in the different watersheds is likely influenced by differences in source areas, geochemical evolution, groundwater flow paths and residence time, local stratigraphy, or some combination thereof.