Paramecium calkinsi was isolated from a tidal marsh in which the salinity fluctuated widely on a daily basis. In the laboratory, this ciliate survived for days in sea water ranging in osmotic strength from 10 to 2,000 mOsm and divided in nutritive media of 1,000 mOsm or less. When transferred from 750 to 250 mOsm, cells swelled but regained 78% of the original volume within 60 min and the original volume within 1 day. Cells acclimated to 250 mOsm and transferred to 750 mOsm shrank, regained 40% of the original volume in 60 min, and regained little more volume during the next 24 hr. Free amino acids (FAA), principally proline and alanine, are osmolytes in P. calkinsi. In cells that have been acclimated for more than 1 month, Pro is undetectable at 10 mOsm but at 250 mOsm is present in substantial amounts and is still higher at 750 mOsm. Ala is found in cells at all three salinities and increases dramatically with increasing salinity. A complex pattern of amino acid changes occurs during the 4 hr following a transfer from 250 to 750 mOsm, resulting in a marked increase in Ala but no change in Pro. Thus the metabolic changes that lead to the increased FAA levels of acclimated cells are apparently long-term and complex. After transfer of cells from 750 to 250 mOsm there is a rapid and selective loss of Pro and Ala from the cells to the medium.