This study intends to bridge the gap between global- and local-scale hydrological studies in the Amazon basin by assessing the hydrological response of the Negro basin. The large basin model from the Institute of Hydraulic Research (MGB-IPH hydrological model) has been used to simulate the hydrological processes over the basin during the period 1997-2006. The model was forced with a precipitation field for the Amazon basin derived from the Hybam observatory and climatological data provided by NCEP. Calibration and validation procedures were developed based on daily discharge datasets from 22 gauge stations. In addition, this paper focusses on ENVISAT spatial altimetry data from 27 virtual stations (VS). The spatial altimetry datasets were used as a complement to the model validation. For each computational cell, water heights could be derived from a robust discharge × height relationship generalized to most parts of the basin. The modelled discharges and water heights feature adequate performance levels at gauge and VS along the main river and tributaries with drainage areas varying from 5900 to 712 500 km2. Nash-Sutcliffe coefficients of modelled discharges varied from 0.47 to 0.94 and correlation coefficients of water heights averaged 0.86 for the entire basin. According to the water balance provided by the model, the amount of precipitation received over the basin is 7.2 mm day-1 during the study period with an evapotranspiration (ET) rate of 3.2 mm day-1. The model could also capture the different ET rates over the basin, as presented in previous studies. Results suggest relatively low ET values in the Northern basin, in the Roraima State, of about 3.1 mm day-1, and higher values near Manaus (3.8 mm day-1). © 2010 John Wiley & Sons, Ltd.