Twelve volunteers participated in a study designed to measure the overnight corneal edema response with a variety of hydrogel contact lenses. During the study four subjects (5 eyes) experienced a contact lens related acute red eye (CLARE) reaction, which manifested as severe ocular pain, photophobia, corneal infiltration, and conjunctival hyperemia. An additional five subjects (7 eyes) developed corneal infiltrates only. Twelve eyes (of 9 subjects) showed no response. Upon microbiological examination of the contact lenses and storage solutions, gram-negative bacteria were isolated in large amounts. The bacteria were identified as Serratia marcescens, Pseudomonas putida, and Pseudomonas aeruginosa. Significantly greater numbers of bacteria were isolated from contact lenses of subjects who experienced CLARE than from the other subjects (P = 0.005) and from the contact lenses of subjects who experienced an adverse reaction (CLARE or infiltrates) than from the other subjects (P < 0.001). The contaminating bacteria are thought to have been introduced to the lens storage vials as a result of lens handling and subsequent failure to disinfect lenses. This study draws attention to the possible contribution of contaminated lenses and storage cases in contact lens related acute inflammation and specifically implicates gram-negative bacteria, in particular Pseudomonas spp. and Serratia spp., in the inducement of acute inflammatory reactions such as CLARE.