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Sedimentological, mineralogical and geochemical analyses of sediment cores from 9 m-deep, saline Laguna Miscanti, Chile (23 degrees 44'S, 67 degrees 46'W, 4140 m a.s.l.) together with high-resolution seismic profiles provide a mid to late Holocene time series of regional environmental change in the Atacama Altiplano constrained by (210)pb and conventional C-14 dating. The mid Holocene was the most arid interval since the last glacial maximum, as documented by subaerial exposure and formation of hardgrounds on a playa surface. Extremely low lake levels during the mid Holocene appear consistent with lower effective moisture recorded at other sites along the Altiplano and in the Amazon Basin. Termination of this arid period represented a major shift in the regional environmental dynamics and inaugurated modern atmospheric conditions. The cores show a progressive upward increase in effective moisture interrupted by numerous century-scale drier periods of various intensities and durations that characterize a fluctuating late Holocene climate. In spite of chronological uncertainties, the major environmental changes seem to correlate with the available paleorecords from the region providing a coherent account of effective moisture variability in the tropical highlands of South America.