Interpretations of state and trends in lake water quality are generally based on measurements from one or more stations that are considered representative of the response of the lake ecosystem. The objective of this study is to examine how these interpretations may be influenced by station location in a large lake. We addressed this by analyzing trends in water quality variables collected monthly from eight monitoring stations along a transect from the central lake to the north in Lake Taihu (area about 2,338 km(2)), China, from October 1991 to December 2011. The parameters examined included chlorophyll a (Chl a), total nitrogen (TN), and total phosphorus (TP) concentrations, and Secchi disk depth (SD). The individual variables were increasingly poorly correlated among stations along the transect from the central lake to the north, particularly for Chl a and TP. The timing of peaks in individual variables was also dependent on station location, with spectral analysis revealing a peak at annual frequency for the central lake station but absence of, or much reduced signal, at this frequency for the near-shore northern station. Percentage annual change values for each of the four variables also varied with station and indicated general improvement in water quality at northern stations, particularly for TN, but little change or decline at central lake stations. Sediment resuspension and tributary nutrient loads were considered to be responsible for some of the variability among stations. Our results indicate that temporal trends in water quality may be station specific in large lakes and that calculated whole-lake trophic status trends or responses to management actions may be specific to the station(s) selected for monitoring and analysis. These results have important implications for efficient design of monitoring programs that are intended to integrate the natural spatial variability of large lakes.