The influence of molecular weight on the elimination kinetics of the potential vitreous substitute hydroxypropyl methylcellulose (HPMC) was studied using solutions of equal viscosity (15,000 cps) of HPMC of molecular weight 86,000 daltons (HPMC 86,000) and HPMC of molecular weight 120,000 daltons (HPMC 120,000). Three days after gas vitrectomy of the right eyes of 64 rabbits, the gas was replaced by 0.5 ml of HPMC solution (2.5% HPMC 86,000 in 39 and 2% HPMC 120,000 solution in 25); HPMC concentration was determined immediately afterwards and 7, 14, 30, 60 and 90 days later by the diphenylamine method, the left eyes being used as blanks. HPMC elimination exhibited order one kinetics, with a half life of 10.4 days for HPMC 86,000 and 38.4 days for HPMC 120,000. These results suggest that by choosing HPMC of suitable molecular weight it may be possible to control the residence time of the polymer in the vitreous cavity.