Medicine Lake is a small (165 ha), relatively shallow (average 7.3 m), intermediate elevation (2,036 m) lake located within the summit caldera of Medicine Lake volcano, Siskiyou County, California, USA. Sediment cores and high-resolution bathymetric and seismic reflection data were collected from the lake during the fall of 1999 and 2000. Sediments were analyzed for diatoms, pollen, density, grain size (sand/mud ratio), total organic carbon (TOC), and micro-scale fabric analysis. Using both ¹⁴C (AMS) dating and tephrochronology, the basal sediments were estimated to have been deposited about 11,400 cal year BP, thus yielding an estimated average sedimentation rate of about 20.66 cm/1,000 year. The lowermost part of the core (11,400–10,300 cal year BP) contains the transition from glacial to interglacial conditions. From about 11,000–5,500 cal year BP, Medicine Lake consisted of two small, steep-sided lakes or one lake with two steep-sided basins connected by a shallow shelf. During this time, both the pollen (Abies/Artemisia ratio) and the diatom (Cyclotella/Navicula ratio) evidences indicate that the effective moisture increased, leading to a deeper lake. Over the past 5,500 years, the pollen record shows that effective moisture continued to increase, and the diatom record indicates fluctuations in the lake level. The change in the lake level pattern from one of the increasing depths prior to about 6,000 cal year BP to one of the variable depths may be related to changes in the morphology of the Medicine Lake caldera associated with the movement of magma and the eruption of the Medicine Lake Glass Flow about 5,120 cal year BP. These changes in basin morphology caused Medicine Lake to flood the shallow shelf which surrounds the deeper part of the lake. During this period, the Cyclotella/Navicula ratio and the percent abundance of Isoetes vary, suggesting that the level of the lake fluctuated, resulting in changes in the shelf area available for colonization by benthic diatoms and Isoetes. These fluctuations are not typical of the small number of low-elevation Holocene lake records in the region, and probably reflect the hydrologic conditions unique to Medicine Lake.