Germ-free and conventional guinea pigs have been conjunctivally challenged with a topical immunogen, ie, albumin, and a topical nonnecrotizing toxic agent, ie, acacia extract. Following immunogenic challenge, germ-free guinea pigs demonstrated appreciably more severe anterior ocular inflammation than conventional animals, which correlated with higher humoral antibody titers. Similarly, germ-free animals demonstrated more severe inflammation when challenged with the toxic agent, acacia. In this circumstance, disease severity correlated with serum γ-globulin levels. These studies readily demonstrate the superiority of germ-free guinea pigs in acute toxicity testing.