The sequential effects of intravenously administered mannitol and oral isosorbide on intraocular pressure, serum osmolality, sodium, and total solids were measured in normal volunteers. Various dose regimens were used to provide optimal schedules for clinical testing. Additionally, a useful correlation between sequential changes in serum and changes of intraocular pressure was sought, but not found. Although both drugs produced prompt intraocular pressure reduction and serum osmolality elevation, only mannitol caused depression of total serum solids and sodium concentrations. These differing effects of the two drugs are ascribed to differing routes of administration and volumes of distribution in body fluids. The 75-gm dose of each drug was well tolerated and effective in reducing intraocular pressure for a minimum of 90 minutes. This dose range appears optimal for clinical testing.