Observations show that the standard precipitation index (SPI) over the southern Amazon region decreased in the period of 1970–1999 by 0.32 per decade, indicating an increase in dry conditions. Simulations of constant pre-industrial climate with recent climate models indicate a low probability ( p =0%) that the trends are due to internal climate variability. When the 23 models are forced with either anthropogenic factors or both anthropogenic and external natural factors, approximately 13% of sampled 30-year SPI trends from the models are found to be within the range of the observed SPI trend at 95% confidence level. This suggests a possibility of anthropogenic and external forcing of climate change in the southern Amazon. On average, the models project no changes in the frequency of occurrence of low SPI values in the future; however, those models which produce more realistic SPI climatology, variability and trend over the period 1970–1999 show more of a tendency towards more negative values of SPI in the future. The analysis presented here suggests a potential anthropogenic influence on Amazon drying, which warrants future, more in-depth, study.