The in vitro dissolution and the relative ocular bioavailability of high- and low-melting phenylephrine oxazolidines (HMP and LMP) from a nonaqueous suspension (silicone fluid) were compared. Stability-indicating HPLC assays were developed for evaluation of the prototype formulations, in which a normal-phase HPLC method was necessary for analysis of PO, while a reverse-phase HPLC method was required for analysis of the primary degradation product, phenylephrine (PE), following its separation from the formulation using a short silica gel column. PO was formulated as an ophthalmic suspension in silicone fluid (20 cs) because of its property of undergoing rapid hydrolysis in aqueous media. An experimental test system for measuring the dissolution characteristics of a water-immiscible multiparticulate suspension was designed to obtain the dissolution profiles of suspensions of HMP and LMP. The dissolution rates, which were nearly identical for LMP and HMP, were obtained assuming a quasi-infinite reservoir. A reverse-phase HPLC assay with fluorescence detection was used for measuring the concentrations of PE in aqueous humor and corneal samples. Statistical analysis of the bioavailability data showed that suspensions containing HMP and LMP were equal in extent of absorption following a single topical application to the rabbit eye. The results correlated well with the in vitro dissolution rates of the suspensions of HMP and LMP.