Long-term trends in the rate of depletion of hypolimnetic dissolved oxygen (DO) are documented for ionically enriched hypereutrophic Onondaga Lake, New York, for the 1978-2002 interval. Depletion rates, represented as areal hypolimnetic oxygen deficits (AHOD, g m Ϫ2 d
Ϫ1), are calculated on the basis of weekly DO profiles of 1-m resolution and estimates of coincident inputs of DO from overlying layers driven by vertical mixing. Vertical mixing inputs of DO are important in this system, representing from 15% to 37% (mean 25%) of AHOD. Interannual variations in hypolimnetic temperatures have comparatively minor (Ϯ6%) effects on AHOD. AHOD decreased 49%, from an average of 2.12 g m Ϫ2 d Ϫ1 for the 1978-1986 interval, to an average of 1.08 g m Ϫ2 d Ϫ1 for the 1997-2002 interval. This decrease was driven by an abrupt decrease in the deposition of particulate organic carbon into the hypolimnion starting in 1987. The magnitude of the decrease in AHOD closes reasonably well with decreases in both primary production in the trophogenic zone and organic carbon deposition to the tropholytic zone. The time course of the decrease in AHOD is consistent with localization of oxygen-demanding processes within the lake sediments, reflecting the progression of sediment diagenesis.